Non-clinical Applications Research Articles

Traditional Renal Biomarkers and New Approaches to Diagnostics

Traditional biomarkers of renal disease have a number of limitations, whether evaluating veterinary patients or performing preclinical toxicity studies. Serum creatinine and urea nitrogen are affected by nonrenal influences that limit their usefulness for detecting small but significant decreases in glomerular filtration rate (GFR) in veterinary patients. These nonrenal influences can be more controlled in preclinical studies than in clinical patients; however, because of its high functional reserve, these estimates of GFR are insensitive for detecting kidney injury prior to loss of a substantial proportion of functioning nephrons. Urine biomarkers can be highly sensitive for tubular or glomerular injury that might lead to irreversible damage to the nephron. Several proteins are qualified by the Food and Drug Administration for nonclinical application as urinary biomarkers of drug-induced nephrotoxicity, and many of these also have preliminary data supporting their usefulness for kidney injury in dogs and cats. In addition to these relatively recently identified biomarkers, efforts are underway to discover new renal biomarkers using a variety of techniques including liquid chromatography-mass spectrometry and small RNA sequencing. Ultimately, the interplay between preclinical studies and clinical patients in discovery and validation of renal biomarkers is critical to their successful implementation.

Crossing Boundaries in Schizotypy Research: An Introduction to the Special Supplement

For nearly 6 decades, the schizotypy construct has served as a conceptual guide for understanding the phenotypic and clinical variability associated with schizophrenia-spectrum vulnerability. Despite the impact of schizotypy on academic research, the public burden of schizophrenia-spectrum pathology has not diminished over time, and it remains poorly understood with no cures, few treatments, and heavy stigma from the lay public. Following on the success of the 2013 Lemanic Workshop on Schizotypy, the International Consortium on Schizotypy Research (ICSR) was formed to address these needs by accelerating scientific discovery of schizophrenia-spectrum pathology. The ICSR convened its 2017 meeting in Beijing China with the theme of Crossing Borders. This included a focus on expanding schizotypy research across 5 domains across: Academic disciplinary borders (promoting brain and genetics/genomics research), clinical borders (promoting clinical and non-clinical applications), geographic borders (promoting cross-cultural research), laboratory borders (promoting big and small data collaborations), and methodology borders (promoting emotion, cognition and behavior research using novel methods). This special supplement provides the highlights from this meeting and related work, including 3 theoretical and position articles, 7 research articles, and 1 invited commentary.

Psychometric properties and accuracy of the European Portuguese version of the Pittsburgh Sleep Quality Index in clinical and non-clinical samples

To assess the reliability and validity concerning the formal European Portuguese version of the Pittsburgh Sleep Quality Index [PSQI (EP)], its accuracy, and optimal cut-off point. N = 564 volunteers (18–80 years old) recruited in several settings (e.g., university campuses; work place; home; sleep consultations), agreed to complete the PSQI (EP). Subgroups completed additional measures: Insomnia Severity Index (ISI), STOP-Bang, Glasgow Sleep Effort Scale, or responded to a supplementary question about perceived sleep problems. As to internal consistency, Cronbach’s α = 0.75. Principal component analysis revealed a unidimensional structure. Six PSQI (EP) components and total scores were able to discriminate individuals who did versus did not describe having any sleep problem; all PSQI (EP) scores were significantly higher (denoting poorer quality) in participants suffering from a sleep disorder. Most Cohen’s d values showed large magnitude associations. PSQI (EP) and ISI scores were highly correlated, but no significant correlations were found considering STOP-Bang. ROC analysis confirmed an optimal cut-off point > 5 of the PSQI (EP) to detect self-reported poor/good sleepers in non-clinical settings. To discriminate non-clinical from clinical sleep patients, the optimal cutoff was > 7, and AUC = 0.94. The European Portuguese version of the PSQI performs as a reliable, valid, and accurate measure of overall sleep quality in Portuguese participants. Furthermore, results suggest that PSQI (EP) can discriminate poor sleepers in non-clinical settings, in addition to demonstrating high clinical accuracy in signaling potential sleep-disorder cases. In conclusion, the PSQI (EP) is a suitable tool to assess general sleep quality in Portuguese participants, both for clinical or non-clinical applications.

Augmented Reality Technology Using Microsoft HoloLens in Anatomic Pathology.

Context Augmented reality (AR) devices such as the Microsoft HoloLens have not been well used in the medical field. Objective To test the HoloLens for clinical and nonclinical applications in pathology. Design A Microsoft HoloLens was tested for virtual annotation during autopsy, viewing 3D gross and microscopic pathology specimens, navigating whole slide images, telepathology, as well as real-time pathology-radiology correlation. Results Pathology residents performing an autopsy wearing the HoloLens were remotely instructed with real-time diagrams, annotations, and voice instruction. 3D-scanned gross pathology specimens could be viewed as holograms and easily manipulated. Telepathology was supported during gross examination and at the time of intraoperative consultation, allowing users to remotely access a pathologist for guidance and to virtually annotate areas of interest on specimens in real-time. The HoloLens permitted radiographs to be coregistered on gross specimens and thereby enhanced locating important pathologic findings. The HoloLens also allowed easy viewing and navigation of whole slide images, using an AR workstation, including multiple coregistered tissue sections facilitating volumetric pathology evaluation. Conclusions The HoloLens is a novel AR tool with multiple clinical and nonclinical applications in pathology. The device was comfortable to wear, easy to use, provided sufficient computing power, and supported high-resolution imaging. It was useful for autopsy, gross and microscopic examination, and ideally suited for digital pathology. Unique applications include remote supervision and annotation, 3D image viewing and manipulation, telepathology in a mixed-reality environment, and real-time pathology-radiology correlation.

Bone Age: A Handy Tool for Pediatric Providers.

Pediatricians have relied on methods for determining skeletal maturation for >75 years. Bone age continues to be a valuable tool in assessing children's health. New technology for bone age determination includes computer-automated readings and assessments obtained from alternative imaging modalities. In addition, new nonclinical bone age applications are evolving, particularly pertaining to immigration and children's rights to asylum. Given the significant implications when bone ages are used in high-stake decisions, it is necessary to recognize recently described limitations in predicting accurate age in various ethnicities and diseases. Current methods of assessing skeletal maturation are derived from primarily white populations. In modern studies, researchers have explored the accuracy of bone age across various ethnicities in the United States. Researchers suggest there is evidence that indicates the bone ages obtained from current methods are less generalizable to children of other ethnicities, particularly children with African and certain Asian backgrounds. Many of the contemporary methods of bone age determination may be calibrated to individual populations and hold promise to perform better in a wider range of ethnicities, but more data are needed.

Simultaneous functional near-infrared spectroscopy and electroencephalography for monitoring of human brain activity and oxygenation: a review.

.Multimodal monitoring has become particularly common in the study of human brain function. In this context, combined, synchronous measurements of functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG) are getting increased interest. Because of the absence of electro-optical interference, it is quite simple to integrate these two noninvasive recording procedures of brain activity. fNIRS and EEG are both scalp-located procedures. fNIRS estimates brain hemodynamic fluctuations relying on spectroscopic measurements, whereas EEG captures the macroscopic temporal dynamics of brain electrical activity through passive voltages evaluations. The “orthogonal” neurophysiological information provided by the two technologies and the increasing interest in the neurovascular coupling phenomenon further encourage their integration. This review provides, together with an introduction regarding the principles and future directions of the two technologies, an evaluation of major clinical and nonclinical applications of this flexible, low-cost combination of neuroimaging modalities. fNIRS–EEG systems exploit the ability of the two technologies to be conducted in an environment or experimental setting and/or on subjects that are generally not suited for other neuroimaging modalities, such as functional magnetic resonance imaging, positron emission tomography, and magnetoencephalography. fNIRS–EEG brain monitoring settles itself as a useful multimodal tool for brain electrical and hemodynamic activity investigation.

MHealth: Mobile Technologies to Virtually Bring the Patient Into an Oncology Practice.

Accompanied by the change in the traditional medical landscape, advances in wireless technology have led to the development of telehealth or mobile health (mHealth), which offers an unparalleled opportunity for health care providers to continually deliver high-quality care. This revolutionary shift makes the patient the consumer of health care and empowers patients to be the driving force of management of their own health through mobile devices and wearable technology. This article presents an overview of technology as it pertains to clinical practice considerations. Telemedicine is changing the way clinical care is delivered without regard for proximity to the patient, whereas nonclinical telehealth applications affect distance education for consumers or clinicians, meetings, research, continuing medical education, and health care management. Technology has the potential to reduce administrative burdens and improve both efficiency and quality of care delivery in the clinic. Finally, the potential for telehealth approaches as cost-effective ways to improve adherence to treatment is explored. As telehealth advances, health care providers must understand the fundamental framework for applying telehealth strategies to incorporate into successful clinical practice.

MHealth: Mobile Technologies to Virtually Bring the Patient Into an Oncology Practice

Accompanied by the change in the traditional medical landscape, advances in wireless technology have led to the development of telehealth or mobile health (mHealth), which offers an unparalleled opportunity for health care providers to continually deliver high-quality care. This revolutionary shift makes the patient the consumer of health care and empowers patients to be the driving force of management of their own health through mobile devices and wearable technology. This article presents an overview of technology as it pertains to clinical practice considerations. Telemedicine is changing the way clinical care is delivered without regard for proximity to the patient, whereas nonclinical telehealth applications affect distance education for consumers or clinicians, meetings, research, continuing medical education, and health care management. Technology has the potential to reduce administrative burdens and improve both efficiency and quality of care delivery in the clinic. Finally, the potential for telehealth approaches as cost-effective ways to improve adherence to treatment is explored. As telehealth advances, health care providers must understand the fundamental framework for applying telehealth strategies to incorporate into successful clinical practice.

Acquisition, Visualization and Potential Applications of 3D Data in Anatomic Pathology.

Although human anatomy and histology are naturally three-dimensional (3D), commonly used diagnostic and educational tools are technologically restricted to providing two-dimensional representations (e.g. gross photography and glass slides). This limitation may be overcome by employing techniques to acquire and display 3D data, which refers to the digital information used to describe a 3D object mathematically. There are several established and experimental strategies to capture macroscopic and microscopic 3D data. In addition, recent hardware and software innovations have propelled the visualization of 3D models, including virtual and augmented reality. Accompanying these advances are novel clinical and non-clinical applications of 3D data in pathology. Medical education and research stand to benefit a great deal from utilizing 3D data as it can change our understanding of complex anatomical and histological structures. Although these technologies are yet to be adopted in routine surgical pathology, forensic pathology has embraced 3D scanning and model reconstruction. In this review, we intend to provide a general overview of the technologies and emerging applications involved with 3D data.

An investigation of the suitability of Artificial Neural Networks for the prediction of core and local skin temperatures when trained with a large and gender-balanced database

Neural networks have been proven to successfully predict the results of complex non-linear problems in a variety of research fields, including medical research. Yet there is paucity of models utilising intelligent systems in the field of thermoregulation. They are under-utilized for predicting seemingly random physiological responses and in particular never used to predict local skin temperatures; or core temperature with a large dataset. In fact, most predictive models in this field (non-artificial intelligence based) focused on predicting body temperature and average skin temperature using relatively small gender-unbalanced databases or data from thermal dummies due to a lack of larger datasets.This paper aimed to address these limitations by applying Artificial Intelligence to create predictive models of core body temperature and local skin temperature (specifically at forehead, chest, upper arms, abdomen, knees and calves) while using a large and gender-balanced experimental database collected in office-type situations.A range of Neural Networks were developed for each local temperature, with topologies of 1–2 hidden layers and up to 20 neurons per layer, using Bayesian and the Levemberg-Marquardt back-propagation algorithms, and using various sets of input parameters (2520 NNs for each of the local skin temperatures and 1760 for the core temperature, i.e. a total of 19400 NNs). All topologies and configurations were assessed and the most suited recommended. The recommended Neural Networks trained well, with no sign of over-fitting, and with good performance when predicting unseen data. The recommended Neural Network for each case was compared with previously reported multi-linear models. Core temperature was avoided as a parameter for local skin temperatures as it is impractical for non-contact monitoring systems and does not significantly improve the precision despite it is the most stable parameter. The recommended NNs substantially improve the predictions in comparison to previous approaches. NN for core temperature has an R-value of 0.87 (81% increase), and a precision of ±0.46°C for an 80% CI which is acceptable for non-clinical applications. NNs for local skin temperatures had R-values of 0.85-0.93 for forehead, chest, abdomen, calves, knees and hands, last two being the strongest (increase of 72% for abdomen, 63% for chest, and 32% for calves and forehead). The precision was best for forehead, chest and calves, with about ±1.2°C, which is similar to the precision of existent average skin temperature models even though the average value is more stable.

Patients' and healthcare providers' perceptions of a mobile portal application for hospitalized patients.

BackgroundHospital-based patient portals have the potential to better inform and engage patients in their care. We sought to assess patients’ and healthcare providers’ perceptions of a hospital-based portal and identify opportunities for design enhancements.MethodsWe developed a mobile patient portal application including information about the care team, scheduled tests and procedures, and a list of active medications. Patients were offered use of tablet computers, with the portal application, during their hospitalization. We conducted semi-structured interviews of patients and provider focus groups. Text from transcribed interviews and focus groups was independently coded by two investigators using a constant comparative approach. Codes were reviewed by a third investigator and discrepancies resolved via consensus.ResultsOverall, 18 patients completed semi-structured interviews and 21 providers participated in three focus groups. Patients found information provided by the portal to be useful, especially regarding team members and medications. Many patients described frequent use of games and non-clinical applications and felt the tablet helped them cope with their acute illness. Patients expressed a desire for additional detail about medications, test results, and the ability to record questions. Providers felt the portal improved patient engagement, but worried that additional features might result in a volume and complexity of information that could be overwhelming for patients. Providers also expressed concern over an enhanced portal’s impact on patient-provider communication and workflow.ConclusionsOptimizing a hospital-based patient portal will require attention to type, timing and format of information provided, as well as the impact on patient-provider communication and workflow.Electronic supplementary materialThe online version of this article (doi:10.1186/s12911-016-0363-7) contains supplementary material, which is available to authorized users.

Use of nonhuman primates for the development of bioengineered female reproductive organs.

Nonhuman primates (NHPs) have been widely used in reproductive biology, neuroscience, and drug development since a number of primate species are phylogenetically close to humans. In this review, we summarize the use of NHPs for nonclinical application in the reproductive system disorders including the loss or failure of an organ or tissue. Causes of infertility include congenital aplasia and acquired disorders of the reproductive organs. In addition, anti-cancer treatments can deplete ovarian follicles, leading to premature ovarian failure, infertility and long-term health risks. Along with a limited supply of human reproductive organs, anatomic/physiologic similarities to humans support the need for NHP models (New-World monkeys such as the common marmoset and Old-World monkeys such as cynomolgus and rhesus monkeys) to promote the advances in female infertility studies. For maintaining and executing animal studies using NHP, special protocols including animal care, anesthetic protocol, surgical technique, and immunosuppressive protocol are necessary. With a growing interest in the potential therapies such as endometrial tissue engineering, and ovary/follicle cryopreservation and grafting in Korea, this review can be useful in selecting appropriate animal models and can bridge between nonclinical studies and clinical applications by providing detailed information on the use of NHPs in the field of reproductive organ disorders.

Old to new ligand-binding assay method modifications.

This article aims to address approaches to ensuring method changes for regulated ligand-binding assays of biologics drugs from old to newer formats and technology are properly understood, characterized and validated to meet current industry expectations and regulatory requirements. Sections in the chapter will include descriptions of different formats of ligand-binding assays, reasons that may drive updating of methods and procedures for qualifying method changes for immunoassays that are designed to support PK and immunogenicity analyses for clinical and nonclinical applications. Case studies from the authors' experience, as well as literature references will be provided as examples of challenges, as well as providing guidance of when and how to provide smooth transitions of older methods to newer, more robust or sensitive methods as reagents or technology are available.

The Different Faces of the Pancreatic Islet.

Type 1 diabetes (T1D) patients who receive pancreatic islet transplant experience significant improvement in their quality-of-life. This comes primarily through improved control of blood sugar levels, restored awareness of hypoglycemia, and prevention of serious and potentially life-threatening diabetes-associated complications, such as kidney failure, heart and vascular disease, stroke, nerve damage, and blindness. Therefore, beta cell replacement through transplantation of isolated islets is an important option in the treatment of T1D. However, lasting success of this promising therapy depends on durable survival and efficacy of the transplanted islets, which are directly influenced by the islet isolation procedures. Thus, isolating pancreatic islets with consistent and reliable quality is critical in the clinical application of islet transplantation.Quality of isolated islets is important in pre-clinical studies as well, as efforts to advance and improve clinical outcomes of islet transplant therapy have relied heavily on animal models ranging from rodents, to pigs, to nonhuman primates. As a result, pancreatic islets have been isolated from these and other species and used in a variety of in vitro or in vivo applications for this and other research purposes. Protocols for islet isolation have been somewhat similar across species, especially, in mammals. However, given the increasing evidence about the distinct structural and functional features of human and mouse islets, using similar methods of islet isolation may contribute to inconsistencies in the islet quality, immunogenicity, and experimental outcomes. This may also contribute to the discrepancies commonly observed between pre-clinical findings and clinical outcomes. Therefore, it is prudent to consider the particular features of pancreatic islets from different species when optimizing islet isolation protocols.In this chapter, we explore the structural and functional features of pancreatic islets from mice, pigs, nonhuman primates, and humans because of their prevalent use in nonclinical, preclinical, and clinical applications.

Whole slide imaging in pathology: advantages, limitations, and emerging perspectives

Significant technologic gains have led to the adoption of innovative digital imaging solutions in pathology. Whole slide imaging (WSI), which refers to scanning of conventional glass slides in order to produce digital slides, is the most recent imaging modality being employed by pathology departments worldwide. WSI continues to gain traction among pathologists for diagnostic, educational, and research purposes. This article provides a technologic review of WSI platforms and covers clinical and nonclinical pathology applications of these imaging systems. Barriers to adoption of WSI include limiting technology, image quality, problems with scanning all materials (eg, cytology slides), cost, digital slide storage, inability to handle high-throughput routine work, regulatory barriers, ergonomics, and pathologists' reluctance. Emerging issues related to clinical validation, standardization, and forthcoming advances in the field are also addressed.

Luminol-based chemiluminescent signals: clinical and non-clinical application and future uses.

Chemiluminescence (CL) is an important method for quantification and analysis of various macromolecules. A wide range of CL agents such as luminol, hydrogen peroxide, fluorescein, dioxetanes and derivatives of oxalate, and acridinium dyes are used according to their biological specificity and utility. This review describes the application of luminol chemiluminescence (LCL) in forensic, biomedical, and clinical sciences. LCL is a very useful detection method due to its selectivity, simplicity, low cost, and high sensitivity. LCL has a dynamic range of applications, including quantification and detection of macro and micromolecules such as proteins, carbohydrates, DNA, and RNA. Luminol-based methods are used in environmental monitoring as biosensors, in the pharmaceutical industry for cellular localization and as biological tracers, and in reporter gene-based assays and several other immunoassays. Here, we also provide information about different compounds that may enhance or inhibit the LCL along with the effect of pH and concentration on LCL. This review covers most of the significant information related to the applications of luminol in different fields.

Fan/cone beam CT: visualisation and applications for non-clinical X-ray imaging

Computed tomography (CT) for non-clinical applications is constantly evolving in many different fields, from industry, laboratory and metrology applications. The Technological Center AIMEN, in collaboration with the University of Santiago de Compostela, has implemented a dual-detector computed tomography system. A specific visualisation tool has been developed including 3D rendering and image reconstruction, following the modular capabilities of the CT system. Software capabilities include CT reconstruction for different geometries, special filtering, higher computer memory requirements, basic knowledge extraction, etc., resulting in flexible software with possibilities for further applications development. This new tool is adapted to the emerging needs of an open CT system which is built in a modular configuration to answer new challenges, as those for dimensional metrology (improving its spatial resolution and image quality) and specific analysis for non-destructive testing.

The acute side effects of bright light therapy: a placebo-controlled investigation.

Despite the emergence of numerous clinical and non-clinical applications of bright light therapy (LT) in recent decades, the prevalence and severity of LT side effects have not yet been fully explicated. A few adverse LT effects—headache, eye strain, irritability, and nausea—have been consistently reported among depressed individuals and other psychiatric cohorts, but there exists little published evidence regarding LT side effects in non-clinical populations, who often undergo LT treatment of considerably briefer duration. Accordingly, in the present study we examined, in a randomized sample of healthy young adults, the acute side effects of exposure to a single 30-minute session of bright white light (10,000 lux) versus dim red light (< 500 lux). Across a broad range of potential side effects, repeated-measures analyses of variance revealed no significant group-by-time (Pre, Post) interactions. In other words, bright light exposure was not associated with a significantly higher incidence of any reported side effect than was the placebo control condition. Nevertheless, small but statistically significant increases in both eye strain and blurred vision were observed among both the LT and control groups. Overall, these results suggest that the relatively common occurrence of adverse side effects observed in the extant LT literature may not fully extend to non-clinical populations, especially for healthy young adults undergoing LT for a brief duration.

Electrochemical Biosensors Based on ZnO Nanostructures to Measure Intracellular Metal Ions and Glucose

Zinc oxide (ZnO) nanostructures have attracted much interest for intracellular electrochemical measurements because of its large surface area, and its biocompatible properties. To design intracellular biosensors for metal ions and glucose, we grew ZnO nanorods on the tip of borosilicate glass capillaries (0.7µm in diameter) and characterized the nano-scale structure with field-emission scanning electron microscopy and high-resolution transmission electron microscopy. The ZnO nanorods were functionalized accordingly for intracellular free metal ions or glucose measurements. Selectivity was achieved by using a metal-ion selective plastic membrane or glucose oxidase enzyme for glucose measurements. These functionalized ZnO nanorods showed high sensitivity and good biocompatibility for intracellular environments. Human adipocytes and frog oocytes were used for determinations of intracellular free metal ions and glucose concentrations. In this review, we discuss the simple and direct approach for intracellular measurements using ZnO nanostructure-based potentiometric biosensors for clinical and nonclinical applications. The performance of ZnO nanostructure-based intracellular sensor can be improved through engineering of morphology, effective surface area, functionality, and adsorption/desorption capability. This study paves the way to find applications in biomedicine by using this simple and miniaturized biosensing device.

Recent progress in nanosensors for sensitive detection of biomolecules

Developing sensitive, rapid, and cost-effective methods for detection of biomolecules is important for both clinical and numerous non-clinical applications. During the last two decades, functional nanomaterials with unique physical and chemical properties have provided significant advantages for biological detection. In this feature article, we introduce recent progress in nanobiosensor development by exploiting the optical, electrical and catalytic properties of a range of nanomaterials, with a focus on gold nanoparticles, carbon nanotubes, graphene and carbon dots. In addition, the perspectives on future opportunities and unsolved challenges are also discussed.