Blood contains a range of protein biomarkers that could be used in the early detection of disease. To achieve this, however, requires sensors capable of detecting (with high reproducibility) biomarkers at concentrations one million times lower than the concentration of the other blood proteins. Here, we show that a sandwich assay that combines mechanical and optoplasmonic transduction can detect cancer biomarkers in serum at ultralow concentrations. A biomarker is first recognized by a surface-anchored antibody and then by an antibody in solution that identifies a free region of the captured biomarker. This second antibody is tethered to a gold nanoparticle that acts as a mass and plasmonic label; the two signatures are detected by means of a silicon cantilever that serves as a mechanical resonator for 'weighing' the mass of the captured nanoparticles and as an optical cavity that boosts the plasmonic signal from the nanoparticles. The capabilities of the approach are illustrated with two cancer biomarkers: the carcinoembryonic antigen and the prostate specific antigen, which are currently in clinical use for the diagnosis, monitoring and prognosis of colon and prostate cancer, respectively. A detection limit of 1 × 10(-16) g ml(-1) in serum is achieved with both biomarkers, which is at least seven orders of magnitude lower than that achieved in routine clinical practice. Moreover, the rate of false positives and false negatives at this concentration is extremely low, ∼10(-4).
Ellipsometry was used to investigate the influence of ionic strength (I) and pH on the adsorption of bovine serum albumin (BSA) or beta-lactoglobulin (BLG) onto preabsorbed layers of two polycations: poly(diallyldimethylammonium chloride) (PDADMAC) or poly(4-vinylpyridine bromide) quaternized with linear aliphatic chains of two (QPVP-C2) or five (QPVP-C5) carbons. Comparisons among results for the three polycations reveal hydrophobic interactions, while comparisons between BSA and BLG-proteins of very similar isoelectric points (pI)-indicate the importance of protein charge anisotropy. At pH close to pI, the ionic strength dependence of the adsorbed amount of protein (Gamma) displayed maxima in the range 10 < I < 25 mM corresponding to Debye lengths close to the protein radii. Visualization of protein charge by Delphi suggested that these ionic strength conditions corresponded to suppression of long-range repulsion between polycations and protein positive domains, without diminution of short-range attraction between polycation segments and locally negative protein domains, in a manner similar to the behavior of PE-protein complexes in solution. (1-4) This description was consistent with the disappearance of the maxima at pH either above or below pI. In the former case, Gamma values decrease exponentially with I(1/2), due to screening of attractions, while in the latter case adsorption of both proteins decreased at low I due to strong repulsion. Close to or below pI both proteins adsorbed more strongly onto QPVP-C5 than onto QPVP-C2 or PDADMAC due to hydrophobic interactions with the longer alkyl group. Above pI, the adsorption was more pronounced with PDADMAC because these chains may assume more loosely bound layers due to lower linear charge density.
With the urbanisation of the population in developing countries and the process of
globalisation, Chagas has become an emerging disease in the urban areas of endemic
and non-endemic countries. In 2006, it was estimated that the prevalence of Chagas
disease among the general Bolivian population was 6.8%. The aim of the present study
was to determine the prevalence of Trypanosoma cruzi infection among
Bolivian immigrants living in São Paulo, Brazil. This study had a sample of 633
volunteers who were randomly selected from the clientele of primary care units
located in the central districts of São Paulo, Brazil. Infection was detected by two
different ELISA assays with epimastigote antigens, followed by an immunoblot with
trypomastigote antigens as a confirmatory test. The prevalence of the infection was
4.4%. Risk factors independently associated with the infection were: a history of
rural jobs in Bolivia, knowledge of the vector involved in transmission, and having
relatives with Chagas disease. Brazil has successfully eliminated household vector
transmission of T. cruzi, as well as its transmission by blood
transfusion. The arrival of infected immigrants represents an additional challenge to
primary care clinics to manage chronic Chagas disease, its vertical transmission, and
the blood derivatives and organ transplant programs.
BACKGROUND: Pressure pain threshold (PPT) is decreased in several musculoskeletal disorders, giving indirect evidence regarding pain status. Despite the fact that PPT has been already proven to be reliable in patients with acute conditions, there is great variability of methods and results observed within studies, and only a few evidences confirming its reliability in chronic conditions. OBJECTIVE: The objective of this study was to determine the test-retest reliability of PPT in the neck and low back regions to discriminate individuals with neck or low back pain from healthy individuals. Additionally, one secondary aim was to establish the minimum detectable change (MDC) and the standard error of measurement for future clinical studies and interventions. METHODS: In this reliability study, 74 individuals (15 individuals from the neck pain and 17 from the neck control group; 21 individuals from the low back pain and 21 from the low back control group). PPT was measured in the neck region (suboccipital, trapezius and supraspinal muscles) and in the lower back region (paraspinal muscles in the levels of L1, L3 and L5). Intrarater reliability was assessed using intraclass correlation coeficient and Bland-Altman. RESULTS: Excellent intra-rater reliability was observed for both (ICC of 0.874 for the neck pain versus ICC of 0.895 in neck control group; ICC of 0.932 for the low back pain group versus ICC of 0.839 for the control group). A small bias was observed for all groups (-0.08 for the neck pain group versus 0.10 in the control group; and 0.32 in low back pain group versus 0.44 in the control group). Minimum detectable change of 0.63 kgf of neck pain and 1.21 kgf of low back pain was calculated. It was found difference in PPT between pain and control groups (p< 0.05). CONCLUSION: It may be suggested that the protocol with PPT is reliable and able to discriminate individuals with and without neck and low back pain with a minor measurement error. Therefore, this method may be used to detect possible progress after interventions in patients with neck or low back pain.
A quartz crystal microbalance method with dissipation (QCM-D) and attenuated total reflection Fourier-transform infrared (ATR-FTIRS) spectroscopy were used to study the adsorption of L-cysteine (L-Cys) on Pt. Through QCM-D, it was possible to verify that the viscoelastic properties of the adsorbed species play an important role in the adsorption, rendering Sauerbrey's equation inapplicable. The modelling of QCM-D data exposed two different processes for the adsorption reaction. The first one had an activation time and is fast, whereas the second is slow. These processes were also resolved by ATR-FTIRS and identified to be water and anion adsorption preceded by L-Cys adsorption. Both techniques reveal that the degree of surface coverage is pH dependent. Spectroscopic data indicate that the conformation of L-Cys changes with pH and that the structures do not fully agree with those proposed in literature for other metallic surfaces. The assembling of the adsorbed monolayer appeared to be very fast, and it was not possible to determine or quantify this kinetics. The conformation is also controlled by applied potential, and the anion adsorption and interfacial water depends on the conformation of the adsorbed molecules.
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