Clinical Diagnostic Instruments Research Articles

1805-LB: Attenuation of Niacin-Induced Skin Flushing Response—A Potential Clinical Adjunctive Diagnostic Instrument for Diabetic Peripheral Neuropathy

1805-LB: Attenuation of Niacin-Induced Skin Flushing Response—A Potential Clinical Adjunctive Diagnostic Instrument for Diabetic Peripheral Neuropathy

Multispectral imaging via feature selection: A frugal innovation approach for pathogen identification

In order to develop an affordable clinical diagnostic instrument for use in more decentralized settings, we have assessed the feasibility to move from hyperspectral to multispectral imaging via parsimonious feature selection. The targeted application is the label-free identification at the species-level of uropathogens from images of bacterial colonies on their growth support. We show that the number of predictors (i.e., discrete spectral channels), can be dramatically reduced from 240 to less than 10 channels with limited performance loss. The impact of bandwidth is also investigated to consider the high degree of redundancy of raster images obtained by diffuse reflectance and propose a suitable design for a simple filter wheel based solution. Targeting the 8 most prevalent bacterial species responsible for > 80% of urinary tract infections, up to 94% of correct identification rate was reached using only 4 spectral windows.

A How to Guide: Clinical Population Test Development and Authorization of MALDI-ToF Mass Spectrometry-Based Screening Tests for Viral Infections.

Applying MALDI-ToF mass spectrometry as a clinical diagnostic test for viruses is different from that of bacteria, fungi and other micro-organisms. This is because the systems biology of viral infections, the size and chemical nature of specific viral proteins and the mass spectrometry biophysics of how they are quantitated are fundamentally different. The analytical challenges to overcome when developing a clinical MALDI-ToF mass spectrometry tests for a virus, particularly human pathogenic enveloped viruses, are sample enrichment, virus envelope disruption, optimal matrix formulation, optimal MALDI ToF MS performance and optimal spectral data processing/bioinformatics. Primarily, the instrument operating settings have to be optimized to match the nature of the viral specific proteins, which are not compatible with setting established when testing for bacterial and many other micro-organisms. The capacity to be a viral infection clinical diagnostic instrument often stretches current mass spectrometers to their operational design limits. Finally, all the associated procedures, from sample collection to data analytics, for the technique have to meet the legal and operational requirement for often high-throughput clinical testing. Given the newness of the technology, clinical MALDI ToF mass spectrometry does not fit in with standard criteria applied by regulatory authorities whereby numeric outputs are compared directly to similar technology tests that have already been authorized for use. Thus, CLIA laboratory developed test (LDT) criteria have to be applied. This article details our experience of developing a SAR-CoV-2 MALDI-ToF MS test suitable for asymptomatic carrier infection population screening.

Serum concentration of zinc is elevated in clinically stable bipolar disorder patients.

BackgroundBipolar disorder (BD) is a chronic psychiatric disorder characterized by recurrent mood episodes interspersed with euthymic periods. A growing number of studies have indicated that zinc plays an important role in coordinating immune responses, as well as being involved in synaptic transmission. In the current study, we set out to measure serum levels of zinc in a meticulously phenotyped cohort of 121 euthymic BD subjects and 30 matched controls.MethodsSerum levels of zinc were measured by photometry. To assess the interplay between zinc levels and immune activation in BD, we measured serum levels of high‐sensitive C‐reactive protein (hsCRP) levels by immunoturbidimetric assay, and serum levels of monocyte chemoattractant protein‐1 (MCP‐1), chitinase 3‐like protein 1 (YKL‐40), and soluble cluster of differentiation 14 (sCD14) by electrochemiluminescence enzyme‐linked immunosorbent assays. The baseline clinical diagnostic instrument for BD was the Affective Disorder Evaluation, and executive functioning was assessed by using the Delis–Kaplan Executive Function System.ResultsControlling for potential confounding factors, BD patients displayed increased serum levels of zinc unrelated to hsCRP, MCP‐1, YKL‐40, and sCD14 levels. Serum levels of zinc did not associate with executive functioning or measurements of disease severity.DiscussionThis study suggests that the zinc homeostasis is disturbed in BD and that this dyshomeostasis is not related to ongoing mood symptoms or immune activation. Of note, serum levels were increased and hence do not support continuous zinc supplementation in BD.

Prevention of Mental Health Disorders Using Internet- and Mobile-Based Interventions: A Narrative Review and Recommendations for Future Research.

Although psychological interventions might have a tremendous potential for the prevention of mental health disorders (MHD), their current impact on the reduction of disease burden is questionable. Possible reasons include that it is not practical to deliver those interventions to the community en masse due to limited health care resources and the limited availability of evidence-based interventions and clinicians in routine practice, especially in rural areas. Therefore, new approaches are needed to maximize the impact of psychological preventive interventions. Limitations of traditional prevention programs could potentially be overcome by providing Internet- and mobile-based interventions (IMIs). This relatively new medium for promoting mental health and preventing MHD introduces a fresh array of possibilities, including the provision of evidence-based psychological interventions that are free from the restraints of travel and time and allow reaching participants for whom traditional opportunities are not an option. This article provides an introduction to the subject and narratively reviews the available evidence for the effectiveness of IMIs with regard to the prevention of MHD onsets. The number of randomized controlled trials that have been conducted to date is very limited and so far it is not possible to draw definite conclusions about the potential of IMIs for the prevention of MHD for specific disorders. Only for the indicated prevention of depression there is consistent evidence across four different randomized trial trials. The only trial on the prevention of general anxiety did not result in positive findings in terms of eating disorders (EDs), effects were only found in post hoc subgroup analyses, indicating that it might be possible to prevent ED onset for subpopulations of people at risk of developing EDs. Future studies need to identify those subpopulations likely to profit from preventive. Disorders not examined so far include substance use disorders, bipolar disorders, stress-related disorders, phobic disorders and panic disorder, obsessive–compulsive disorder, impulse-control disorders, somatic symptom disorder, and insomnia. In summary, there is a need for more rigorously conducted large scale randomized controlled trials using standard clinical diagnostic instruments for the selection of participants without MHD at baseline and the assessment of MHD onset. Subsequently, we discuss future directions for the field in order to fully exploit the potential of IMI for the prevention of MHD.

Diagnostic criteria for temporomandibular disorders (DC/TMD): interexaminer reliability of the Finnish version of Axis I clinical diagnoses.

Recently, updated diagnostic criteria for temporomandibular disorders (DC/TMD) were published to assess TMD in a standardised way in clinical and research settings. The DC/TMD protocol has been translated into Finnish using specific cultural equivalency procedures. To assess the interexaminer reliability using the Finnish translations of the DC/TMD-FIN Axis I clinical diagnostic assessment instruments. Reliability assessment data were collected during a 1-day DC/TMD Examiner Training Course at the University of Turku, Finland, in collaboration with the International DC/TMD Training and Calibration Center in Malmö University. Clinical TMD examinations according to the Finnish pre-final version of the DC/TMD Axis I assessment protocol were performed by four experienced TMD specialists on altogether 16 models. Kappa coefficient, overall percentage agreement (%A) as well as positive (PA) and negative (NA) agreements were used to define the reliability. Myofascial pain with referral, headache attributed to TMD and disc displacement (DD) without reduction without limited opening showed excellent kappa values (range 0·87-1·00). Fair-to-good reliability was observed for diagnoses of myalgia (k = 0·67), arthralgia (k = 0·71) and DD with reduction (k = 0·64). The PA was high for all pain-related diagnoses and DD without reduction without limited opening (medians ≥83%), and acceptable for DD with reduction (median 67%). The NA was high (medians ≥87%) for all DC/TMD diagnoses, except for myalgia which showed acceptable NA (median 75%). The %A was high for all assessed diagnoses (medians >85%). The findings of this study showed DC/TMD-FIN Axis I to demonstrate sufficiently high reliability for pain-related TMD diagnoses.

Maternal depression and personality traits in association with child neuropsychological and behavioral development in preschool years: Mother-child cohort (Rhea Study) in Crete, Greece

BackgroundPoor perinatal maternal mental health has been linked with negative outcomes on early child development; however, the importance of maternal personality has been neglected thus far. We aimed to examine the effects of antenatal and postnatal maternal mental health, including assessment of maternal personality characteristics, on child neuropsychological and behavioral development at preschool years in a population based mother-child cohort (Rhea Study) in Crete, Greece. MethodSelf-reported measures of maternal depression (EPDS), trait anxiety (STAI-Trait) and personality traits (EPQ-R) were assessed in a sample of 288 women at 28–32 weeks of gestation. A larger sample of 642 mothers completed the EPDS scale at 8 weeks postpartum. Children's neuropsychological (MSCA) and behavioral (ADHDT and SDQ) development were assessed at 4 years of age. Linear regression analyses were used to estimate the associations between the exposures and outcomes of interest after adjustment for potential confounders. ResultsRegarding child neuropsychological development, increased postnatal depressive symptoms were associated with child's perceptual performance, whereas increased maternal psychoticism was linked with child's motor ability at 4 years of age. Furthermore, elevated levels of maternal depression during pregnancy and postpartum, and the predisposing personality characteristics of trait anxiety and neuroticism, were associated with children's behavioral difficulties. LimitationsA clinical diagnostic instrument for maternal mental health was not used and assessment of children's behavior was based on maternal report. ConclusionThese findings suggest that poor perinatal maternal mental health and an adverse personality profile may be associated with impaired child neuropsychological and behavioral development at preschool years.

Dopaminergic Neurodegeneration in the Mouse Is Associated with Decrease of Viscoelasticity of Substantia Nigra Tissue.

The biomechanical properties of brain tissue are altered by histopathological changes due to neurodegenerative diseases like Parkinson's disease (PD). Such alterations can be measured by magnetic resonance elastography (MRE) as a non-invasive technique to determine viscoelastic parameters of the brain. Until now, the correlation between histopathological mechanisms and observed alterations in tissue viscoelasticity in neurodegenerative diseases is still not completely understood. Thus, the objective of this study was to evaluate (1) the validity of MRE to detect viscoelastic changes in small and specific brain regions: the substantia nigra (SN), midbrain and hippocampus in a mouse model of PD, and (2) if the induced dopaminergic neurodegeneration and inflammation in the SN is reflected by local changes in viscoelasticity. Therefore, MRE measurements of the SN, midbrain and hippocampus were performed in adult female mice before and at five time points after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin hydrochloride (MPTP) treatment specifically lesioning dopaminergic neurons in the SN. At each time point, additional mice were utilized for histological analysis of the SN. After treatment cessation, we observed opposed viscoelastic changes in the midbrain, hippocampus and SN with the midbrain showing a gradual rise and the hippocampus a distinct transient increase of viscous and elastic parameters, while viscosity and–to a lesser extent—elasticity in the SN decreased over time. The decrease in viscosity and elasticity in the SN was paralleled by a reduced number of neurons due to the MPTP-induced neurodegeneration. In conclusion, MRE is highly sensitive to detect local viscoelastic changes in specific and even small brain regions. Moreover, we confirmed that neuronal cells likely constitute the backbone of the adult brain mainly accounting for its viscoelasticity. Therefore, MRE could be established as a new potential instrument for clinical evaluation and diagnostics of neurodegenerative diseases.

Breastfeeding and postpartum depression: Assessing the influence of breastfeeding intention and other risk factors

BackgroundRisk and protective factors for postpartum depression have been extensively studied, and in recent studies an association between breastfeeding and maternal mood has been reported. The present retrospective, cross-sectional study was conducted to evaluate the association between breastfeeding-related variables and postpartum depression (based on Edinburgh Postnatal Depression Scale threshold criteria) within the context of other known risk factors. MethodBreastfeeding information, demographic information, and scores on the Edinburgh Postnatal Depression Scale were examined from the Canadian Maternity Experience Survey. This survey contains data collected from 6421 Canadian mothers between October 2006 and January 2007, and 2848 women between five and seven months postpartum were included in the current analyses. ResultsIn contrast to previous research, logistic regression analyses revealed that when considered within the context of other risk factors, breastfeeding attempt and duration were not associated with postpartum depression at five to seven months postpartum. Although a relationship between the prenatal intention to combination feed and postpartum depression was observed, these variables were no longer related once other potential risk factors were controlled for. Factors that were associated with postpartum depression included lower income, higher perceived stress, lower perceived social support, no history of depression, or no recent history of abuse. LimitationsA clinical diagnostic instrument was not used and variable selection was restricted to data collected as part of this survey. ConclusionThese findings suggest that the association between breastfeeding and postpartum depression reported by previous researchers may in fact be due to alternative risk factors.

A Direct Comparison of Real-World and Virtual Navigation Performance in Chronic Stroke Patients

An increasing number of studies have presented evidence that various patient groups with acquired brain injury suffer from navigation problems in daily life. This skill is, however, scarcely addressed in current clinical neuropsychological practice and suitable diagnostic instruments are lacking. Real-world navigation tests are limited by geographical location and associated with practical constraints. It was, therefore, investigated whether virtual navigation might serve as a useful alternative. To investigate the convergent validity of virtual navigation testing, performance on the Virtual Tubingen test was compared to that on an analogous real-world navigation test in 68 chronic stroke patients. The same eight subtasks, addressing route and survey knowledge aspects, were assessed in both tests. In addition, navigation performance of stroke patients was compared to that of 44 healthy controls. A correlation analysis showed moderate overlap (r = .535) between composite scores of overall real-world and virtual navigation performance in stroke patients. Route knowledge composite scores correlated somewhat stronger (r = .523) than survey knowledge composite scores (r = .442). When comparing group performances, patients obtained lower scores than controls on seven subtasks. Whereas the real-world test was found to be easier than its virtual counterpart, no significant interaction-effects were found between group and environment. Given moderate overlap of the total scores between the two navigation tests, we conclude that virtual testing of navigation ability is a valid alternative to navigation tests that rely on real-world route exposure.

Two dimensions of social anxiety disorder: a pilot study of the Questionnaire for Social Anxiety and Social Competence Deficits for Adolescents.

BackgroundThe Questionnaire for Social Anxiety and Social Competence Deficits for Adolescents (SASKO-J) was developed as an instrument for clinical diagnostics of social anxiety disorder in youths by measuring social anxiety and social deficits in two separate dimensions. The study provides an initial assessment of the scale’s psychometric properties in a clinical sample.MethodThe reliability and validity of the SASKO-J were assessed in a mixed clinical sample of 12- to 19-year-old German adolescents (N = 85; mean age 15.71 years; SD = 1.92; 62.4 % girls). In a second step, the diagnostic validity was evaluated in a clinical sample of 31 adolescent patients with social anxiety disorder (mean age 16.10 years; SD = 1.54; 74.2 % girls) and a sample of 115 German high school students (mean age 15.84 years; SD = 1.65; 60.9 % girls) via Receiver Operating Characteristic (ROC) analysis.ResultsThe internal consistencies of the total scale and the subscales were good to excellent (0.80 ≤ α ≤ 0.96), and the results indicated a good convergent and divergent validity. The ROC analysis revealed a satisfying area under curve (AUC = 0.866), and a cutoff of 41.5 for the SASKO-J total score represented the best balance of sensitivity (0.806) and specificity (0.826).ConclusionsThe results of this pilot study provide initial support for the clinical use of the SASKO-J in the diagnostic process. Future research should address the question of psychometric properties in a social anxiety disorder sample as well as the questionnaire’s sensitivity for detecting change in symptoms during therapy.

Poster #T91 CHILDHOOD ABUSE AND BRIEF LIFE EVENTS IN POSTPARTUM PSYCHOSIS

Risk and protective factors for postpartum depression have been extensively studied, and in recent studies an association between breastfeeding and maternal mood has been reported. The present retrospective, cross-sectional study was conducted to evaluate the association between breastfeeding-related variables and postpartum depression (based on Edinburgh Postnatal Depression Scale threshold criteria) within the context of other known risk factors.Breastfeeding information, demographic information, and scores on the Edinburgh Postnatal Depression Scale were examined from the Canadian Maternity Experience Survey. This survey contains data collected from 6421 Canadian mothers between October 2006 and January 2007, and 2848 women between five and seven months postpartum were included in the current analyses.In contrast to previous research, logistic regression analyses revealed that when considered within the context of other risk factors, breastfeeding attempt and duration were not associated with postpartum depression at five to seven months postpartum. Although a relationship between the prenatal intention to combination feed and postpartum depression was observed, these variables were no longer related once other potential risk factors were controlled for. Factors that were associated with postpartum depression included lower income, higher perceived stress, lower perceived social support, no history of depression, or no recent history of abuse.A clinical diagnostic instrument was not used and variable selection was restricted to data collected as part of this survey.These findings suggest that the association between breastfeeding and postpartum depression reported by previous researchers may in fact be due to alternative risk factors.

From Faulty Biochemical Assumptions to Poor Diagnostic Performance: Reflections on the Failure of DNA Microarrays to Become a Reliable Clinical Diagnostic Tool

Since their inception about two decades ago, DNA microarrays have been considered as a great hope in translational research and personalized medicine. Although DNA microarrays for gene expression profiling proved to be an indispensable tool in the laboratory settings, their applications as an instrument for clinical diag nostics have not yet produced tangible results. In this paper, we convey the idea that, apart from notoriously poor reproducibility and complexities of experimental validations, there exist other reasons hindering clinical application of DNA microarrays. These reasons are rooted in the very core of the DNA microarrays methodology, that is, in faulty biochemical assumptions underlying microarray measurements. A key premise the microarray measurements are based on is that mRNA abundances harvested from the e ukaryotic cytoplasm are indicative of the activity levels of corresponding genes. There are at least two reasons why this premise is questionable. First, each transcription is supported by a number of transcription factors expressed by many genes. Due to this reason, relations between the transcription rates of genes and the mRNA abundances are the 'many-to-one', not the 'one-to-on e'; therefore, abnormality in a certain mRNA abundance does not unequivocally indicate abnormality of the gene bearing its comp limentary code. Second, mRNA copy numbers in cytoplasm are regulated by a number of epigenetic factors among which the post-transcriptional mRNA stability is of primary importance. Abnormal concentration of certain mRNA may result from deviant

A Dedicated Low-Cost Fluorescence Microfluidic Device Reader for Point-of-Care Ocular Diagnostics

Microfluidic fluorescence assay devices show great promise as preclinical and clinical diagnostic instruments. Normally, fluorescence signals from microfluidic chips are quantified by analysis of images obtained with a commercial fluorescence microscope. This method is unnecessarily expensive, time consuming, and requires significant operator training, particularly when considering future clinical translation of the technology. In this work, we developed a dedicated low cost fluorescence microfluidic device reader (FMDR) to read sandwich immunofluorescence assay (sIFA) devices configured to detect vascular endothelial growth factor ligand concentrations in ocular fluid samples. Using a series of sIFA calibration standards and a limited set of human ocular fluid samples, we demonstrated that our FMDR reader has similar sensitivity and accuracy to a fluorescence microscope for this task, with significantly lower total cost and reduced reading time. We anticipate that the reader could be used with minor modifications for virtually any fluorescence microfluidic device.

The clinical utility of the Maslach Burnout Inventory in a clinical population.

This replication study examines the use of the Maslach Burnout Inventory (MBI-GS), a self-report questionnaire on burnout, as a clinical diagnostic instrument for measuring clinical burnout. The MBI and Mini International Neuropsychiatric Interview (MINI), a semistructured interview based on classifications in the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994), were administered to 419 outpatients at a Dutch multicenter institution specializing in the treatment of work-related psychological problems. MBI scores indicative of the presence of burnout were compared to the primary DSM-IV diagnosis as established by the MINI. The DSM-IV diagnosis "undifferentiated somatoform disorder" was used as a proxy measure for clinical burnout. The results showed that the psychometric properties of the MBI were good. The factorial validity of the MBI could be confirmed. Several decision rules or cutoff points were assessed to determine the discriminant validity of the MBI. None of these cutoff points proved to be sufficiently discriminable, however. Receiver operating characteristic analyses revealed that the MBI showed the highest sum of sensitivity (78%) and specificity (48%) with a cutoff point of 3.50 on the Exhaustion subscale, with a kappa agreement of .25 with the structured diagnostic interview. The practical implication is that the MBI should not be used by itself as a diagnostic tool in a patient population, because of a resultant high probability of overdiagnosing burnout.

Method development: Raman spectroscopy‐based histopathology of oral mucosa

An earlier and more accurate detection of (small) cancerous and precancerous lesions in the oral cavity is essential to improve the prognosis of oral squamous cell carcinomas. Raman spectroscopy is being pursued as a potential method to realize this improvement, since the technique provides objective information on a biochemical level and can be used for real‐time guidance of the diagnostic procedure.Since oral mucosal tissue is inhomogeneous and comprises different layers and histological structures, a good understanding of the signal contributions of the individual layers and structures is required for an accurate interpretation of in vivo tissue spectra measurement volumes. The aim of this study was to create a standardized method to collect and analyse the spectral contributions of individual histopathological structures in oral mucosa.The method is based on Raman microspectroscopic mapping of unstained frozen tissue sections and subsequent histopathological annotation of the features in the resulting Raman images. The obtained annotated reference spectra were used as input in an unsupervised hierarchical cluster analysis in order to determine the spectral characteristics and variance within one histo(patho)logical structure.The described method resulted in an annotated database of Raman spectral characteristics of individual histopathological structures encountered in oral tissue. This database can be used as input for the development of classification and quantification algorithms, in order to achieve a high specificity and sensitivity for clinical diagnostic instruments. Additionally, this database can be used to optimize the exact location and measurement volume of in vivo measurements. Copyright © 2013 John Wiley & Sons, Ltd.

On-Chip Flow Cytometry: Where is it Now and Where is it Going?

Flow cytometry is a powerful, high-throughput, single-cell characterization and sorting tool, which has a unique capability to provide fast and quantitative analyses of individual cells and physical separation of cells of particular interest from other cells [1]. In flow cytometry, the cell analyses are performed by passing a narrow stream of cells through a focused laser beam at a rate of thousands of cells per second. Information regarding the size, type and content of cells can subsequently be derived through the analyses of the excited fluorescence emission or scattered light arising from each individual cell. In recent years, flow cytometry has rapidly become an indispensable instrument for many clinical diagnostics, ranging from routine blood tests to diagnoses of lethal diseases such as leukemia, respiratory infection and HIV/AIDS. Flow cytometry can screen multiple parameters and can be used for immunophenotyping. This has allowed diagnosis of diseases associated with B lymphocytes [1] and progress in the Human Immunology Project [2]. HIV is also typically monitored using flow cytometry [1]. Additionally, cell-sorting techniques have enabled flow cytometry to become a key tool for studying circulating tumor cells, which have potential in screening for and monitoring cancer [3,4]. With its extraordinary single-cell ana lysis and sorting capabilities, flow cytometry has been used extensively in numerous fields such as molecular biology, pathology, immunology, plant biology and marine biology. Despite their significant impact, current commercial f low cytometry systems have the following drawbacks: high cost, large instrumentation size and the constant requirement of highly trained personnel for maintenance (the latter two resulting from its complex system configuration).

Prevalence of Child Mental Health Problems in Sub-Saharan Africa

To assess the prevalence of child mental health problems in community settings in sub-Saharan Africa. A systematic search of MEDLINE, EMBASE, and PsychInfo, supplemented by tracking of references from identified articles and personal communications with local researchers. Only community-based studies in sub-Saharan Africa that assessed the general psychopathology of children aged 0 to 16 years were included. For each eligible study, the following information was extracted: year of publication, country, population sampled, area type (rural or urban), sampling method and sample size (percentage boys), age range, assessment instrument, informant, diagnostic criteria, and prevalence rates of general psychopathology. Pooled prevalence rate of psychopathology in children, identified by questionnaire and, specifically, by clinical diagnostic instruments. Eleven studies met the inclusion criteria, 10 of which were included in the meta-analysis. The 10 studies provided data for 9713 children from 6 countries, with substantial variation in assessment methods. Overall, 14.3% (95% CI, 13.6%-15.0%) of children were identified as having psychopathology. Studies using screening questionnaires reported higher prevalence rates (19.8%; 95% CI, 18.8%-20.7%) than did studies using clinical diagnostic instruments (9.5%; 8.4%-10.5%). Evidence suggests that considerable levels of mental health problems exist among children and adolescents in sub-Saharan Africa. One in 7 children and adolescents have significant difficulties, with 1 in 10 (9.5%) having a specific psychiatric disorder. There are clear sociodemographic correlates of psychopathology that may place children in areas of greatest deprivation at greatest risk.

Glucose in human serum determined by capillary electrophoresis with glucose micro-biosensor

A glucose micro-biosensor was employed as detector in capillary electrophoresis (CE) for determining the concentration of glucose in human serum. The micro-biosensor was based on the immobilization of the SWNTs-glucose oxidase-chitosan biocomposite at a platinized Au electrode by electrodeposition. The influencing factors including separation voltage, detection potential, pH value, and the concentration of the buffer were studied. Suitable conditions were obtained for the determination of glucose: running buffer, 25 mM PBS (pH 8.0); separation field strength, 250 V cm(-1); detection potential, 0.80 V vs. saturated calomel electrode. Under optimized detection conditions, glucose responded linearly from the range of 5 μM to 1 mM with a correlation coefficient of 0.9986 for the injection voltage of 5.0 kV and injection time of 10 s. The concentration limit of detection of the method was 1 μM (S/N = 3). The micro-biosensor exhibited good stability and durability in the analytical procedures. The relative standard deviation of the migration time and peak current were 1.7% and 2.6%, respectively. Glucose in human serum from two healthy individuals and two diabetics was successfully determined, giving a good prospect for a new clinical diagnostic instrument.

Do DNA Microarrays Tell the Story of Gene Expression?

Poor reproducibility of microarray measurements is a major obstacle to their application as an instrument for clinical diagnostics. In this paper, several aspects of poor reproducibility are analyzed. All of them belong to the category of interpretive weaknesses of DNA microarray technology. First, the attention is drawn to the fact that absence of the information regarding post-transcriptional mRNA stability makes it impossible to evaluate the level of gene activity from the relative mRNA abundances, the quantities available from microarray measurements. Second, irreducible intracellular variability with persistent patterns of stochasticity and burstiness put natural limits to reproducibility. Third, strong interactions within intracellular biomolecular networks make it highly problematic to build a bridge between transcription rates of individual genes and structural fidelity of their genetic codes. For these reasons, the microarray measurements of relative mRNA abundances are more appropriate in laboratory settings as a tool for scientific research, hypotheses generating and producing the leads for subsequent validation through more sophisticated technologies. As to clinical settings, where firm conclusive diagnoses, not the leads for further experimentation, are required, microarrays still have a long way to go until they become a reliable instrument in patient-related decision making.