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Diagnostics, Volume 6, Issue 4 (December 2016)

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Research

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Open AccessArticle Exploring the Limits of Cell Adhesion under Shear Stress within Physiological Conditions and beyond on a Chip
Diagnostics 2016, 6(4), 38; doi:10.3390/diagnostics6040038
Received: 10 August 2016 / Revised: 16 September 2016 / Accepted: 13 October 2016 / Published: 21 October 2016
Cited by 2 | PDF Full-text (1957 KB) | HTML Full-text | XML Full-text
Abstract
Cell adhesion processes are of ubiquitous importance for biomedical applications such as optimization of implant materials. Here, not only physiological conditions such as temperature or pH, but also topographical structures play crucial roles, as inflammatory reactions after surgery can diminish osseointegration. In this
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Cell adhesion processes are of ubiquitous importance for biomedical applications such as optimization of implant materials. Here, not only physiological conditions such as temperature or pH, but also topographical structures play crucial roles, as inflammatory reactions after surgery can diminish osseointegration. In this study, we systematically investigate cell adhesion under static, dynamic and physiologically relevant conditions employing a lab-on-a-chip system. We screen adhesion of the bone osteosarcoma cell line SaOs-2 on a titanium implant material for pH and temperature values in the physiological range and beyond, to explore the limits of cell adhesion, e.g., for feverish and acidic conditions. A detailed study of different surface roughness Rq gives insight into the correlation between the cells’ abilities to adhere and withstand shear flow and the topography of the substrates, finding a local optimum at Rq = 22 nm. We use shear stress induced by acoustic streaming to determine a measure for the ability of cell adhesion under an external force for various conditions. We find an optimum of cell adhesion for T = 37 °C and pH = 7.4 with decreasing cell adhesion outside the physiological range, especially for high T and low pH. We find constant detachment rates in the physiological regime, but this behavior tends to collapse at the limits of 41 °C and pH 4. Full article
(This article belongs to the Special Issue Lab-on-a-Chip Based Diagnostics)
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Open AccessArticle Endogenous Intoxication and Saliva Lipid Peroxidation in Patients with Lung Cancer
Diagnostics 2016, 6(4), 39; doi:10.3390/diagnostics6040039
Received: 8 August 2016 / Revised: 7 November 2016 / Accepted: 9 November 2016 / Published: 16 November 2016
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Abstract
This research was aimed at a search for regularities in changes to parameters of endogenous intoxication and saliva lipid peroxidation in patients with lung cancer, non-malignant lung diseases, and apparently healthy people. All patients went through saliva sampling at an amount of 1
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This research was aimed at a search for regularities in changes to parameters of endogenous intoxication and saliva lipid peroxidation in patients with lung cancer, non-malignant lung diseases, and apparently healthy people. All patients went through saliva sampling at an amount of 1 mL. A concentration of malondialdehyde (MDA) was measured according to a reaction with thiobarbituric acid, and a level of middle molecules (MM) was measured with UV spectroscopy at 254 and 280 nm, while the content of lipid peroxidation products was measured according to a degree of heptane extract light absorption at wavelengths of 220, 232, 278, and 400 nm. It has been revealed that in the context of lung cancer, the level of diene conjugates decreases, increasing the level of triene conjugates, Schiff’s bases, and MM. As a tumor grows, there is a decrease in the level of lipid peroxidation primary products and an increase in endotoxemia phenomena. The process is more apparent when going from local to locally advanced disease states. The nature of the MDA change is nonlinearly associated with tumor progression. The findings might be used to optimize traditional aids of diagnostics, in disease state forecasting, in treatment monitoring, etc. Full article
(This article belongs to the Special Issue Oral Fluid-Based Molecular Diagnostics)
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Open AccessArticle The Effect of Exercise on Salivary Viscosity
Diagnostics 2016, 6(4), 40; doi:10.3390/diagnostics6040040
Received: 29 September 2016 / Revised: 4 November 2016 / Accepted: 8 November 2016 / Published: 16 November 2016
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Abstract
A common experience after exercise is the presence of a thick and sticky saliva layer on the oral surfaces, which causes a feeling of a dry mouth. Since the salivary mucin MUC5B is responsible for the visco-elastic behavior of saliva, in the present
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A common experience after exercise is the presence of a thick and sticky saliva layer on the oral surfaces, which causes a feeling of a dry mouth. Since the salivary mucin MUC5B is responsible for the visco-elastic behavior of saliva, in the present study we explored the effect of exercise on both the salivary viscosity and the secretion of MUC5B in saliva. Twenty healthy dental students performed an aerobic exercise by cycling for 15 min on cycle-ergometers at a heart rate of 130–140 beats per minute. Saliva was collected at three time points: before exercise, immediately after exercise and after 30 min recovery. Salivary flow rate, viscosity, amylase activity, total protein, carbohydrate and MUC5B concentration were determined. Salivary flow rate, protein and amylase did not change significantly. Immediately after exercise, the salivary viscosity and carbohydrate concentration were significantly higher than at baseline and after 30 min recovery. Immediately after exercise, the MUC5B concentration was significantly higher than after 30 min recovery. It is concluded that the presence of thick saliva after exercise is at least partially due to an increased secretion of MUC5B. Full article
(This article belongs to the Special Issue Oral Fluid-Based Molecular Diagnostics)
Open AccessArticle Gingival Crevicular Fluid as a Novel Potential Source of Biomarkers Distinguishes Pubertal from Post-Pubertal Subjects
Diagnostics 2016, 6(4), 41; doi:10.3390/diagnostics6040041
Received: 30 September 2016 / Revised: 7 November 2016 / Accepted: 9 November 2016 / Published: 17 November 2016
Cited by 1 | PDF Full-text (1773 KB) | HTML Full-text | XML Full-text
Abstract
Detection of pubertal growth peak is vital in orthodontic treatment timing and planning. Gingival crevicular fluid (GCF) contains abundant proteins from different sources and has been proven to be an ideal source of biomarkers. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) is an
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Detection of pubertal growth peak is vital in orthodontic treatment timing and planning. Gingival crevicular fluid (GCF) contains abundant proteins from different sources and has been proven to be an ideal source of biomarkers. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) is an advanced technique that can detect low-molecular-weight peptides with high sensitivity and resolution. The aim of this research was to identify novel candidate biomarkers in GCF to help the diagnosis of pubertal growth peak by MALDI-TOF/MS. Results showed that the peak intensities of six peptides were significantly different between two groups: 1660.2 Da, 1783.0 Da, 2912.5 Da, 4178.6 Da, 5064.9 Da, and 6108.9 Da and are considered to be potential candidate biomarkers to identify pubertal growth peak. Further studies are needed to identify sequence information of these candidate biomarkers. Full article
(This article belongs to the Special Issue Oral Fluid-Based Molecular Diagnostics)
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Review

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Open AccessReview The Role of PET/CT Molecular Imaging in the Diagnosis of Recurrence and Surveillance of Patients Treated for Non-Small Cell Lung Cancer
Diagnostics 2016, 6(4), 36; doi:10.3390/diagnostics6040036
Received: 4 May 2016 / Revised: 8 September 2016 / Accepted: 22 September 2016 / Published: 30 September 2016
Cited by 2 | PDF Full-text (2154 KB) | HTML Full-text | XML Full-text
Abstract
Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide and its prognosis remains poor. Molecular imaging with 18F-FDG PET/CT can metabolically characterize the nature of lesions as benign or malignant, allowing a better staging at the diagnosis of
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Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide and its prognosis remains poor. Molecular imaging with 18F-FDG PET/CT can metabolically characterize the nature of lesions as benign or malignant, allowing a better staging at the diagnosis of this kind of patient. This advantage can also be applied in the re-staging due to the suspicion of recurrent disease. Many patients have a recurrence of the disease, including surgically treated patients. In the current context, with new personalized oncological treatments, the surveillance for recurrence and its accurate diagnosis are crucial to improve their survival. In this paper, we revise the current knowledge about the clinical and molecular factors related to the recurrent disease. In the context of new, promising, available personalized treatments, the role of molecular imaging with PET/CT and 18F-FDG and non-18F-FDG radiotracers in the follow-up of NSCLC-treated patients is especially attractive and interesting. Full article
(This article belongs to the Special Issue Positron Emission Tomography (PET) in Cardiology and Oncology)
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Open AccessReview Fluid Biomarkers of Traumatic Brain Injury and Intended Context of Use
Diagnostics 2016, 6(4), 37; doi:10.3390/diagnostics6040037
Received: 27 July 2016 / Revised: 27 September 2016 / Accepted: 30 September 2016 / Published: 18 October 2016
Cited by 1 | PDF Full-text (279 KB) | HTML Full-text | XML Full-text
Abstract
Traumatic brain injury (TBI) is one of the leading causes of death and disability around the world. The lack of validated biomarkers for TBI is a major impediment to developing effective therapies and improving clinical practice, as well as stimulating much work in
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Traumatic brain injury (TBI) is one of the leading causes of death and disability around the world. The lack of validated biomarkers for TBI is a major impediment to developing effective therapies and improving clinical practice, as well as stimulating much work in this area. In this review, we focus on different settings of TBI management where blood or cerebrospinal fluid (CSF) biomarkers could be utilized for predicting clinically-relevant consequences and guiding management decisions. Requirements that the biomarker must fulfill differ based on the intended context of use (CoU). Specifically, we focus on fluid biomarkers in order to: (1) identify patients who may require acute neuroimaging (cranial computerized tomography (CT) or magnetic resonance imaging (MRI); (2) select patients at risk for secondary brain injury processes; (3) aid in counseling patients about their symptoms at discharge; (4) identify patients at risk for developing postconcussive syndrome (PCS), posttraumatic epilepsy (PTE) or chronic traumatic encephalopathy (CTE); (5) predict outcomes with respect to poor or good recovery; (6) inform counseling as to return to work (RTW) or to play. Despite significant advances already made from biomarker-based studies of TBI, there is an immediate need for further large-scale studies focused on identifying and innovating sensitive and reliable TBI biomarkers. These studies should be designed with the intended CoU in mind. Full article
(This article belongs to the Special Issue Biomarkers in Blood 2016)
Open AccessReview Targeted Molecular Imaging in Adrenal Disease—An Emerging Role for Metomidate PET-CT
Diagnostics 2016, 6(4), 42; doi:10.3390/diagnostics6040042
Received: 24 August 2016 / Revised: 8 November 2016 / Accepted: 9 November 2016 / Published: 18 November 2016
Cited by 2 | PDF Full-text (14639 KB) | HTML Full-text | XML Full-text
Abstract
Adrenal lesions present a significant diagnostic burden for both radiologists and endocrinologists, especially with the increasing number of adrenal ‘incidentalomas’ detected on modern computed tomography (CT) or magnetic resonance imaging (MRI). A key objective is the reliable distinction of benign disease from either
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Adrenal lesions present a significant diagnostic burden for both radiologists and endocrinologists, especially with the increasing number of adrenal ‘incidentalomas’ detected on modern computed tomography (CT) or magnetic resonance imaging (MRI). A key objective is the reliable distinction of benign disease from either primary adrenal malignancy (e.g., adrenocortical carcinoma or malignant forms of pheochromocytoma/paraganglioma (PPGL)) or metastases (e.g., bronchial, renal). Benign lesions may still be associated with adverse sequelae through autonomous hormone hypersecretion (e.g., primary aldosteronism, Cushing’s syndrome, phaeochromocytoma). Here, identifying a causative lesion, or lateralising the disease to a single adrenal gland, is key to effective management, as unilateral adrenalectomy may offer the potential for curing conditions that are typically associated with significant excess morbidity and mortality. This review considers the evolving role of positron emission tomography (PET) imaging in addressing the limitations of traditional cross-sectional imaging and adjunctive techniques, such as venous sampling, in the management of adrenal disorders. We review the development of targeted molecular imaging to the adrenocortical enzymes CYP11B1 and CYP11B2 with different radiolabeled metomidate compounds. Particular consideration is given to iodo-metomidate PET tracers for the diagnosis and management of adrenocortical carcinoma, and the increasingly recognized utility of 11C-metomidate PET-CT in primary aldosteronism. Full article
(This article belongs to the Special Issue Positron Emission Tomography (PET) in Cardiology and Oncology)
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Open AccessReview Gold Nanoparticles for Diagnostics: Advances towards Points of Care
Diagnostics 2016, 6(4), 43; doi:10.3390/diagnostics6040043
Received: 25 October 2016 / Revised: 13 November 2016 / Accepted: 18 November 2016 / Published: 22 November 2016
Cited by 1 | PDF Full-text (5789 KB) | HTML Full-text | XML Full-text
Abstract
The remarkable physicochemical properties of gold nanoparticles (AuNPs) have prompted developments in the exploration of biomolecular interactions with AuNP-containing systems, in particular for biomedical applications in diagnostics. These systems show great promise in improving sensitivity, ease of operation and portability. Despite this endeavor,
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The remarkable physicochemical properties of gold nanoparticles (AuNPs) have prompted developments in the exploration of biomolecular interactions with AuNP-containing systems, in particular for biomedical applications in diagnostics. These systems show great promise in improving sensitivity, ease of operation and portability. Despite this endeavor, most platforms have yet to reach maturity and make their way into clinics or points of care (POC). Here, we present an overview of emerging and available molecular diagnostics using AuNPs for biomedical sensing that are currently being translated to the clinical setting. Full article
(This article belongs to the Special Issue Novel Point-of-Care Technologies in Diagnostics)
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Open AccessReview First- and Second-Line Targeted Systemic Therapy in Hepatocellular Carcinoma—An Update on Patient Selection and Response Evaluation
Diagnostics 2016, 6(4), 44; doi:10.3390/diagnostics6040044
Received: 26 July 2016 / Revised: 22 November 2016 / Accepted: 23 November 2016 / Published: 28 November 2016
Cited by 2 | PDF Full-text (206 KB) | HTML Full-text | XML Full-text
Abstract
Advanced hepatocellular carcinoma (HCC) with vascular invasion and/or extrahepatic spread and preserved liver function, according to stage C of the Barcelona Clinic Liver Cancer (BCLC) classification, has a dismal prognosis. The multi-targeted tyrosine-kinase receptor inhibitor (TKI) sorafenib is the only proven active substance
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Advanced hepatocellular carcinoma (HCC) with vascular invasion and/or extrahepatic spread and preserved liver function, according to stage C of the Barcelona Clinic Liver Cancer (BCLC) classification, has a dismal prognosis. The multi-targeted tyrosine-kinase receptor inhibitor (TKI) sorafenib is the only proven active substance in systemic HCC therapy for first-line treatment. In this review, we summarize current aspects in patient selection and management of side effects, and provide an update on response evaluation during first-line sorafenib therapy. Since second-line treatment options have been improved with the successful completion of the RESORCE trial, demonstrating a survival benefit for second-line treatment with the TKI regorafenib, response monitoring during first-line therapy will be critical to deliver optimal systemic therapy in HCC. To this regard, specific side effects, in particular worsening of arterial hypertension and diarrhea, might suggest treatment response during first-line sorafenib therapy; however, clear predictive clinical markers, as well as laboratory test or serum markers, are not established. Assessment of radiologic response according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) is helpful to identify patients who do not benefit from sorafenib treatment. Full article
(This article belongs to the collection Feature Papers)
Open AccessReview Oral Biofluid Biomarker Research: Current Status and Emerging Frontiers
Diagnostics 2016, 6(4), 45; doi:10.3390/diagnostics6040045
Received: 4 October 2016 / Revised: 15 November 2016 / Accepted: 7 December 2016 / Published: 17 December 2016
Cited by 1 | PDF Full-text (233 KB) | HTML Full-text | XML Full-text
Abstract
Salivary diagnostics is a rapidly advancing field that offers clinicians and patients the potential of rapid, noninvasive diagnostics with excellent accuracy. In order for the complete realization of the potential of saliva, however, extensive profiling of constituents must be conducted and diagnostic biomarkers
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Salivary diagnostics is a rapidly advancing field that offers clinicians and patients the potential of rapid, noninvasive diagnostics with excellent accuracy. In order for the complete realization of the potential of saliva, however, extensive profiling of constituents must be conducted and diagnostic biomarkers must be thoroughly validated. This article briefly overviews the process of conducting a study of salivary biomarkers in a patient cohort and highlights the studies that have been conducted on different classes of molecules in the saliva. Emerging frontiers in salivary diagnostics research that may significantly advance the field will also be highlighted. Full article
(This article belongs to the Special Issue Oral Fluid-Based Molecular Diagnostics)
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