Biological Diagnostic Tools Research Articles

Vascularites immunologiques des petits et moyens vaisseaux : physiopathologie et diagnostic biologique

AbstractVasculitis is defined by inflammation of the vascular endothelium, it is rare and difficult to diagnose. This article will only discuss primary non-infectious vasculitis, as is done in the international nomenclature of Chapel Hill, the second version of which aimed to replace the eponymous names of diseases with expressions related to their pathophysiological mechanism or their histological characteristics. This nomenclature of vasculitis takes into account the size of the vessels and the pathophysiological mechanisms which, in the involvement of small and medium-sized vessels, are immunological mechanisms. These are first, vasculitis with immune complex deposition, including cryoglobulinemic vasculitis, vasculitis with IgA deposits, hypocomplementemic urticarial vasculitis (McDuffie’s disease) and vasculitis with anti-glomerular basement membrane Abs (Goodpasture’s disease), and second, vasculitis with anti-neutrophil cytoplasmic Abs (ANCA), including granulomatosis with polyangiitis (formerly Wegener’s syndrome), eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome) and microscopic polyangiitis. In this article, the pathophysiological mechanisms of these immunological vasculitides and the biological diagnostic tools will be developed, allowing biologists to participate in the diagnosis of these rare and frequently severe diseases.

ETUDE COMPARATIVE DE LA PERFORMANCE DIAGNOSTIQUE DES MARQUEURS INDIRECTS D’ALCOOLISATION CHRONIQUE : CDT, GGT ET VGM

ntroduction: gamma glutamyl transferase (GGT) andmean corpuscular volume (MCV) are the traditionalmarkers of chronic alcoholism. For over 30 years,carbohydrate-deficient transferrin (CDT) has been oneof the biological diagnostic tools used in themanagement of alcohol-dependent patients. The aimof this study was to set up a capillary electrophoresisassay for CDT in the Biochemistry Laboratory of theFann Hospital and University Centre, in order to providepractitioners with much more effective diagnostic toolsfor identifying and monitoring alcohol dependence.Materials and methods: The methodology consistedof recruiting patients diagnosed as alcohol-dependentat the Centre de Prise en Charge Intégrée desAddictions de Dakar (CEPIAD) and determining GMV,GGT activity and CDT content. The CDT content wasobtained by capillary electrophoresis and the resultsexpressed as a percentage of total transferrin. Toensure the absence of liver damage, transaminaseactivity was assessed.Results: The results showed that CDT was much moresensitive because it was disturbed in more than halfthe patients, compared with 40% for GGT and 10%for VGM. CDT was elevated in 100% of patientsconsuming more than 1 litre of alcohol. It also appearedthat in the presence of alcoholic hepatitis as evidencedby an ASAT/ALAT ratio > 1, GGT appeared to be moresensitive. The combination of GGT and CDT was moresensitive than either GGT-VGM or CDT-VGM.Conclusion: CDT was a highly relevant parameter inthe diagnosis and monitoring of alcohol-dependentpatients. It is more relevant to combine CDT and GGTthan GGT and VGM, which are traditionally measuredroutinely.Key words: CDT, alcohol dependence, biologicaldiagnosisCorrespondance : Fatoumata Bah,Laboratoire de Toxicologie et Hydrologie de la FMPO de l’UCAD, Dakar.Tel : +221 33 824 65 39.Email : fabah2001@yahoo.fr10

Renal clearable magnetic nanoparticles for magnetic resonance imaging and guided therapy.

Magnetic resonance imaging (MRI) is a non-invasive, radiation-free imaging technique widely used for disease detection and therapeutic evaluation due to its infinite penetration depth. Magnetic nanoparticles (MNPs) have unique magnetic and physicochemical properties, making them ideal as contrast agents for MRI. However, the in vivo toxicity of MNPs, resulting from metal ion leakage and long-term accumulation in the reticuloendothelial system (RES), limits their clinical application. To overcome these challenges, there is considerable interest in the development of renal-clearable MNPs that can be completely cleared through the kidney, reducing retention time and potential toxic risks. In this review, we provide an overview of recent advancements in the development of renal-clearable MNPs for disease imaging and treatment. We discuss the factors influencing renal clearance, summarize the types of renal-clearable MNPs, their synthesis methods, and biomedical applications. This review aims to offer comprehensive information for the design and clinical translation of renal-clearable MNPs. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Diagnostic Tools > Biosensing.

Passive sweat wearable: A new paradigm in the wearable landscape toward enabling "detect to treat" opportunities.

Growing interest over recent years in personalized health monitoring coupled with the skyrocketing popularity of wearable smart devices has led to the increased relevance of wearable sweat-based sensors for biomarker detection. From optimizing workouts to risk management of cardiovascular diseases and monitoring prediabetes, the ability of sweat sensors to continuously and noninvasively measure biomarkers in real-time has a wide range of applications. Conventional sweat sensors utilize external stimulation of sweat glands to obtain samples, however; this stimulation influences the expression profile of the biomarkers and reduces the accuracy of the detection method. To address this limitation, our laboratory pioneered the development of the passive sweat sensor subfield, which allowed for our progress in developing a sweat chemistry panel. Passive sweat sensors utilize nanoporous structures to confine and detect biomarkers in ultra-low sweat volumes. The ability of passive sweat sensors to use smaller samples than conventional sensors enable users with sedentary lifestyles who perspire less to benefit from sweat sensor technology not previously afforded to them. Herein, the mechanisms and strategies of current sweat sensors are summarized with an emphasis on the emerging subfield of passive sweat-based diagnostics. Prospects for this technology include discovering new biomarkers expressed in sweat and expanding the list of relevant detectable biomarkers. Moreover, the accuracy of biomarker detection can be enhanced with machine learning using prediction algorithms trained on clinical data. Applying this machine learning in conjunction with multiplex biomarker detection will allow for a more holistic approach to trend predictions. This article is categorized under: Diagnostic Tools > Diagnostic Nanodevices Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Diagnostic Tools > Biosensing.

Magnetite-based Janus nanoparticles, their synthesis and biomedical applications.

The advent of Janus nanoparticles has been a great breakthrough in the emerging field of nanomaterials. Janus nanoparticles refer to a single structure with two distinct chemical functions on either side. Owing to their asymmetric structures, they can be utilized in a variety of applications where monomorphic particles are insufficient. In the last decade, a wide variety of materials have been employed to fabricate Janus nanoparticles, and due to the great advantages of magnetite (Iron-oxide) NPs, they have been considered as one of the best candidates. With the main benefit of magnetic controlling, magnetite Janus nanoparticles fulfill great promises, especially in biomedical areas such as bioimaging, cancer therapies, theranostics, and biosensing. The intrinsic characteristics of magnetite Janus nanoparticles (MJNPs) even hold great potential in magnetite Janus forms of micro-/nanomotors. Despite the great interest and potential in magnetic Janus NPs, the need for a comprehensive review on MJNPs with a concentration on magnetite NPs has been overlooked. Herein, we present recent advancements in the magnetite-based Janus nanoparticles in the flourishing field of biomedicine. First, the synthesis and fabrication methods of Janus nanoparticles are discussed. Then we will delve into their intriguing biomedical applications, with a separate section for magnetite Janus micro-/nanomotors in biomedicine. And finally, the challenges and future outlook are provided. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Diagnostic Tools > Diagnostic Nanodevices Diagnostic Tools > In Vitro Nanoparticle-Based Sensing.

Generative adversarial network based data augmentation for CNN based detection of Covid-19

Covid-19 has been a global concern since 2019, crippling the world economy and health. Biological diagnostic tools have since been developed to identify the virus from bodily fluids and since the virus causes pneumonia, which results in lung inflammation, the presence of the virus can also be detected using medical imaging by expert radiologists. The success of each diagnostic method is measured by the hit rate for identifying Covid infections. However, the access for people to each diagnosis tool can be limited, depending on the geographic region and, since Covid treatment denotes a race against time, the diagnosis duration plays an important role. Hospitals with X-ray opportunities are widely distributed all over the world, so a method investigating lung X-ray images for possible Covid-19 infections would offer itself. Promising results have been achieved in the literature in automatically detecting the virus using medical images like CT scans and X-rays using supervised artificial neural network algorithms. One of the major drawbacks of supervised learning models is that they require enormous amounts of data to train, and generalize on new data. In this study, we develop a Swish activated, Instance and Batch normalized Residual U-Net GAN with dense blocks and skip connections to create synthetic and augmented data for training. The proposed GAN architecture, due to the presence of instance normalization and swish activation, can deal with the randomness of luminosity, that arises due to different sources of X-ray images better than the classical architecture and generate realistic-looking synthetic data. Also, the radiology equipment is not generally computationally efficient. They cannot efficiently run state-of-the-art deep neural networks such as DenseNet and ResNet effectively. Hence, we propose a novel CNN architecture that is 40% lighter and more accurate than state-of-the-art CNN networks. Multi-class classification of the three classes of chest X-rays (CXR), ie Covid-19, healthy and Pneumonia, is performed using the proposed model which had an extremely high test accuracy of 99.2% which has not been achieved in any previous studies in the literature. Based on the mentioned criteria for developing Corona infection diagnosis, in the present study, an Artificial Intelligence based method is proposed, resulting in a rapid diagnostic tool for Covid infections based on generative adversarial and convolutional neural networks. The benefit will be a high accuracy of lung infection identification with 99% accuracy. This could lead to a support tool that helps in rapid diagnosis, and an accessible Covid identification method using CXR images.

Regulating photochemical properties of carbon dots for theranostic applications.

As a new zero-dimensional carbon-based material, carbon dots (CDs) have attracted extensive attention owing to their advantages such as easy preparation and surface modification, good biocompatibility and water solubility, and tunable photochemical properties. CDs have become one of the most promising nanomaterials in the field of fluorescent sensing, bioimaging, and cancer therapy. How to precisely regulate the photochemical properties, especially the absorption, fluorescence, phosphorescence, reactive oxygen species generation, and photothermal conversion of the CDs, is the key to developing highly efficient phototheranostics for cancer treatment. Although many studies on cancer therapy using CDs have been published, no review has focused on the regulation of photochemical properties of CDs for phototheranostic applications. In this review, we summarized the strategies such as the selection of suitable carbon source, heteroatomic doping, optimum reaction conditions, surface modification, and assembly strategy to efficiently regulate the photochemical properties of the CDs to meet the requirements of different practical applications. This review might provide some valuable insight and new ideas for the development of CDs with excellent phototheranostic performance. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.

Surface-enhanced Raman scattering: An emerging tool for sensing cellular function.

Continuous long‐term intracellular imaging and multiplexed monitoring of biomolecular changes associated with key cellular processes remains a challenge for the scientific community. Recently, surface‐enhanced Raman scattering (SERS) has been demonstrated as a powerful spectroscopic tool in the field of biology owing to its significant advantages. Some of these include the ability to provide molecule‐specific information with exquisite sensitivity, working with small volumes of precious samples, real‐time monitoring, and optimal optical contrast. More importantly, the availability of a large number of novel Raman reporters with narrower full width at half maximum (FWHM) of spectral peaks/vibrational modes than conventional fluorophores has created a versatile palette of SERS‐based probes that allow targeted multiplex sensing surpassing the detection sensitivity of even fluorescent probes. Due to its nondestructive nature, its applicability has been recognized for biological sensing, molecular imaging, and dynamic monitoring of complex intracellular processes. We critically discuss recent developments in this area with a focus on different applications where SERS has been used for obtaining information that remains elusive for conventional imaging methods. Current reports indicate that SERS has made significant inroads in the field of biology and has the potential to be used for in vivo human applications.This article is categorized under:Diagnostic Tools > In Vitro Nanoparticle‐Based SensingNanotechnology Approaches to Biology > Nanoscale Systems in BiologyDiagnostic Tools > BiosensingDiagnostic Tools > In Vivo Nanodiagnostics and Imaging

Subcellular delivery of lipid nanoparticles to endoplasmic reticulum and mitochondria.

Primarily responsible for the biogenesis and metabolism of biomolecules, endoplasmic reticulum (ER) and mitochondria are gradually becoming the targets of therapeutic modulation, whose physiological activities and pathological manifestations determine the functional capacity and even the survival of cells. Drug delivery systems with specific physicochemical properties (passive targeting), or modified by small molecular compounds, polypeptides, and biomembranes demonstrating tropism for ER and mitochondria (active targeting) are able to reduce the nonselective accumulation of drugs, enhancing efficacy while reducing side effects. Lipid nanoparticles feature high biocompatibility, diverse cargo loading, and flexible structure modification, which are frequently used for subcellular organelle-targeted delivery of therapeutics. However, there is still a lack of systematic understanding of lipid nanoparticle-based ER and mitochondria targeting. Herein, we review the pathological significance of drug selectively delivered to the ER and mitochondria. We also summarize the molecular basis and application prospects of lipid nanoparticle-based ER and mitochondria targeting strategies, which may provide guidance for the prevention and treatment of associated diseases and disorders. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Biology-Inspired Nanomaterials > Lipid-Based Structures Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.

Advances of functional nanomaterials for magnetic resonance imaging and biomedical engineering applications.

Functional nanomaterials have been widely used in biomedical fields due to their good biocompatibility, excellent physicochemical properties, easy surface modification, and easy regulation of size and morphology. Functional nanomaterials for magnetic resonance imaging (MRI) can target specific sites in vivo and more easily detect disease-related specific biomarkers at the molecular and cellular levels than traditional contrast agents, achieving a broad application prospect in MRI. This review focuses on the basic principles of MRI, the classification, synthesis and surface modification methods of contrast agents, and their clinical applications to provide guidance for designing novel contrast agents and optimizing the contrast effect. Furthermore, the latest biomedical advances of functional nanomaterials in medical diagnosis and disease detection, disease treatment, the combination of diagnosis and treatment (theranostics), multi-model imaging and nanozyme are also summarized and discussed. Finally, the bright application prospects of functional nanomaterials in biomedicine are emphasized and the urgent need to achieve significant breakthroughs in the industrial transformation and the clinical translation is proposed. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Diagnostic Tools > Diagnostic Nanodevices Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

One stone, many birds: Recent advances in functional nanogels for cancer nanotheranostics.

Inspired by the development of nanomedicine and nanotechnology, more and more possibilities in cancer theranostic have been provided in the last few years. Emerging therapeutic modalities like starvation therapy, chemodynamic therapy, and tumor oxygenation have been integrated with diagnosis, giving a plethora of theranostic nanoagents. Among all of them, nanogels (NGs) show superiority benefiting from their unique attributes: high stability, high water‐absorption, large specific surface area, mechanical strength, controlled responsiveness, and high encapsulation capacity. There have been a vast number of investigations supporting various NGs combining drug delivery and multiple bioimaging techniques, encompassing photothermal imaging, photoacoustic imaging, fluorescent imaging, ultrasound imaging, magnetic resonance imaging, and computed tomography. This review summarizes recent advances in functional NGs for theranostic nanomedicine and discusses the challenges and future perspectives of this fast‐growing field.This article is categorized under:Therapeutic Approaches and Drug Discovery > Emerging TechnologiesTherapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic DiseaseNanotechnology Approaches to Biology > Nanoscale Systems in BiologyDiagnostic Tools > In Vivo Nanodiagnostics and Imaging

What makes carbon nanoparticle a potent material for biological application?

Carbon materials are generally utilized in the form of carbon allotropes and their characteristics are exploited as such or for improving the thermal, electrical, optical, and mechanical properties of other biomaterials. This has now found a broader share in conventional biomaterial space with the generation of nanodiamond, carbon dot, carbon nanoparticles (CNPs), and so forth. With properties of better biocompatibility, intrinsic optical emission, aqueous suspendability, and easier surface conjugation possibilities made CNPs as one of the fore most choice for biological applications especially for use in intracellular spaces. There are various reports available presenting methods of preparing, characterizing, and using CNPs for various biological applications but a collection of information on what makes CNP a suitable biomaterial to achieve those biological activities is yet to be provided in a significant way. Herein, a series of correlations among synthesis, characterization, and mode of utilization of CNP have been incorporated along with the variations in its use as agent for sensing, imaging, and therapy of different diseases or conditions. It is ensembled that how simplified and optimized methods of synthesis is correlated with specific characteristics of CNPs which were found to be suitable in the specific biological applications. These comparisons and correlations among various CNPs, will surely provide a platform to generate new edition of this nanomaterial with improvised applications and newer methods of evaluating structural, physical, and functional properties. This may ensure the eventual use of CNPs for human being for specific need in near future. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Diagnostic Tools > Biosensing Diagnostic Tools > In Vitro Nanoparticle-Based Sensing Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Integration of chemically modified nucleotides with DNA strand displacement reactions for applications in living systems.

Watson-Crick base pairing rules provide a powerful approach for engineering DNA-based nanodevices with programmable and predictable behaviors. In particular, DNA strand displacement reactions have enabled the development of an impressive repertoire of molecular devices with complex functionalities. By relying on DNA to function, dynamic strand displacement devices represent powerful tools for the interrogation and manipulation of biological systems. Yet, implementation in living systems has been a slow process due to several persistent challenges, including nuclease degradation. To circumvent these issues, researchers are increasingly turning to chemically modified nucleotides as a means to increase device performance and reliability within harsh biological environments. In this review, we summarize recent progress toward the integration of chemically modified nucleotides with DNA strand displacement reactions, highlighting key successes in the development of robust systems and devices that operate in living cells and in vivo. We discuss the advantages and disadvantages of commonly employed modifications as they pertain to DNA strand displacement, as well as considerations that must be taken into account when applying modified oligonucleotide to living cells. Finally, we explore how chemically modified nucleotides fit into the broader goal of bringing dynamic DNA nanotechnology into the cell, and the challenges that remain. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Diagnostic Tools > Biosensing.

Embracing nanomaterials' interactions with the innate immune system.

Immunotherapy has firmly established itself as a compelling avenue for treating disease. Although many clinically approved immunotherapeutics engage the adaptive immune system, therapeutically targeting the innate immune system remains much less explored. Nanomedicine offers a compelling opportunity for innate immune system engagement, as many nanomaterials inherently interact with myeloid cells (e.g., monocytes, macrophages, neutrophils, and dendritic cells) or can be functionalized to target their cell-surface receptors. Here, we provide a perspective on exploiting nanomaterials for innate immune system regulation. We focus on specific nanomaterial design parameters, including size, form, rigidity, charge, and surface decoration. Furthermore, we examine the potential of high-throughput screening and machine learning, while also providing recommendations for advancing the field. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Toward nanobioelectronic medicine: Unlocking new applications using nanotechnology.

Bioelectronic medicine aims to interface electronic technology with biological components and design more effective therapeutic and diagnostic tools. Advances in nanotechnology have moved the field forward improving the seamless interaction between biological and electronic components. In the lab many of these nanobioelectronic devices have the potential to improve current treatment approaches, including those for cancer, cardiovascular disorders, and disease underpinned by malfunctions in neuronal electrical communication. While promising, many of these devices and technologies require further development before they can be successfully applied in a clinical setting. Here, we highlight recent work which is close to achieving this goal, including discussion of nanoparticles, carbon nanotubes, and nanowires for medical applications. We also look forward toward the next decade to determine how current developments in nanotechnology could shape the growing field of bioelectronic medicine. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Diagnostic Tools > Biosensing.

Radiolabeling strategies and pharmacokinetic studies for metal based nanotheranostics.

Radiolabeled metal-based nanoparticles (MNPs) have drawn considerable attention in the fields of nuclear medicine and molecular imaging, drug delivery, and radiation therapy, given the fact that they can be potentially used as diagnostic imaging and/or therapeutic agents, or even as theranostic combinations. Here, we present a systematic review on recent advances in the design and synthesis of MNPs with major focuses on their radiolabeling strategies and the determinants of their in vivo pharmacokinetics, and together how their intended applications would be impacted. For clarification, we categorize all reported radiolabeling strategies for MNPs into indirect and direct approaches. While indirect labeling simply refers to the use of bifunctional chelators or prosthetic groups conjugated to MNPs for post-synthesis labeling with radionuclides, we found that many practical direct labeling methodologies have been developed to incorporate radionuclides into the MNP core without using extra reagents, including chemisorption, radiochemical doping, hadronic bombardment, encapsulation, and isotope or cation exchange. From the perspective of practical use, a few relevant examples are presented and discussed in terms of their pros and cons. We further reviewed the determinants of in vivo pharmacokinetic parameters of MNPs, including factors influencing their in vivo absorption, distribution, metabolism, and elimination, and discussed the challenges and opportunities in the development of radiolabeled MNPs for in vivo biomedical applications. Taken together, we believe the cumulative advancement summarized in this review would provide a general guidance in the field for design and synthesis of radiolabeled MNPs towards practical realization of their much desired theranostic capabilities. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Diagnostic Tools > Diagnostic Nanodevices Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Stimuli-activatable nanomedicines for chemodynamic therapy of cancer.

Chemodynamic therapy (CDT) takes the advantages of Fenton-type reactions triggered by endogenous chemical energy to generate highly cytotoxic hydroxyl radicals. As a novel modality for cancer treatment, CDT shows minimal invasiveness and high tumor specificity by responding to the acidic and the highly concentrated hydrogen peroxide microenvironment of tumor. The CDT approach for spatiotemporal controllable reactive oxygen species generation exhibits preferable therapeutic performance and satisfying biosafety. In this review article, we summarized the recent advances of stimuli-activatable nanomedicines for CDT. We also overviewed the strategies for augmenting CDT performance, including increasing the catalytic efficacy through rational design of the nanomaterials, modulating the reaction condition, inputting external energy field, and regulating the tumor microenvironment. Furthermore, we discussed the potential and challenges of stimuli-activatable nanomedicine for clinical translation and future development of CDT. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.

Review of biological diagnostic tools and their applications in geoenvironmental engineering

Biological diagnostic tools are becoming an increasingly important aspect of geoenvironmental problems. Modern geoenvironmental professionals must be able to both understand and exploit biological processes for a variety of applications, ranging from contaminant biodegradation and removal to evaluation and monitoring of environmental quality in and around landfills and landfill cover systems. Advancements in genetics and environmental measurement have yielded a wealth of sophisticated tools to evaluate biological processes in soils, sediments and groundwater. Successful use of these tools requires a keen understanding of the limitations and advantages offered by each. This paper provides an overview of the currently available biological diagnostic tools with an emphasis on their application in geoenvironmental engineering. Limitations and unresolved challenges in successful applications of these tools are also discussed.

Normotensive Incidentally Discovered Pheochromocytomas Display Specific Biochemical, Cellular, and Molecular Characteristics

A number of incidentally discovered pheochromocytomas are not associated with hypertension. The characteristics of normotensive incidentally discovered pheochromocytomas (NIPs) are poorly known. The purpose of this work was to assess the clinical, hormonal, histological, and molecular features of NIPs. This was a retrospective cohort recruited from 2001 to 2011 in 2 tertiary care medical departments. Clinical, biological, and radiological investigations performed in 96 consecutive patients with sporadic unilateral pheochromocytomas were examined; 47 patients had overt pheochromocytomas responsible for hypertension. Among the patients with incidental pheochromocytomas, 28 had hypertension and 21 were normotensive (NIPs). A total of 62 tumors were examined to determine the Pheochromocytoma of the Adrenal Gland Scale Score, and 29 were studied for the expression of 16 genes involved in chromaffin cell function. Tumor size and metaiodobenzylguanidine (MIBG) scintigraphy results were similar for hypertensive pheochromocytomas (HPs) and NIPs. Patients with NIPs displayed reduced summed levels of urinary catecholamines and metanephrines and, more specifically, reduced levels of adrenaline and metadrenaline compared with those of patients with HPs (P < .001). Urinary metanephrines had 98% diagnostic sensitivity in patients with HPs and only 75% in patients with NIPs (P < .01). Tumor diameter positively correlated with the total amount of urinary concentrations of metanephrines in patients with HPs (P < .001) but not in patients with NIPs. NIPs displayed global decreased chromaffin gene expression (reaching significance for 5 of them) and 2 corresponding proteins (phenylethanolamine N-methyltransferase and secretogranin II) and a significant increase in the cellularity, mitotic activity, and presence of atypical mitosis (P < .05). NIPs differ from pheochromocytomas responsible for hypertension and display features of altered chromaffin differentiation. These tumors may be misdiagnosed with the use of the usual biological diagnostic tools.

Is urinary indolyl-3-acryloylglycine a biomarker for autism with gastrointestinal symptoms?

An autism spectrum disorder (ASD) diagnosis is based on clinical behaviours as there are no validated biological diagnostic tools. Indolyl-3-acryloylglycine (IAG) is a chemical produced by gut microflora and there are conflicting reports as to whether urinary levels are elevated in children with ASD compared with controls. Urinary IAG levels in morning urine samples were statistically significantly higher in children with ASD whose caregivers reported the presence of chronic gastrointestinal (GI) disturbance than children with ASD without chronic GI disturbance. Urinary IAG, however, was not statistically significantly higher in children with ASD, compared with siblings or unrelated controls without ASD.