Concordance of International Regulation of Pediatric Health Research.

OBJECTIVE: To assess the comparability of international ethics principles and practices used in regulating pediatric research as a first step in determining whether reciprocal deference for international ethics review is feasible. Prior studies by the authors focused on other aspects of international health research, such as biobanks and direct-to-participant genomic research. The unique nature of pediatric research and its distinctive regulation by many countries warranted a separate study. STUDY DESIGN: A representative sample of 21 countries was selected, with geographical, ethnic, cultural, political, and economic diversity. A leading expert on pediatric research ethics and law was selected to summarize the ethics review of pediatric research in each country. To ensure the comparability of the responses, a 5-part summary of pediatric research ethics principles in the US was developed by the investigators and distributed to all country representatives. The international experts were asked to assess and describe whether principles in their country and the US were congruent. Results were obtained and compiled in the spring and summer of 2022. RESULTS: Some of the countries varied in their conceptualization or description of one or more ethical principles for pediatric research, but overall, the countries in the study demonstrated a fundamental concordance. CONCLUSIONS: Similar regulation of pediatric research in 21 countries suggests that international reciprocity is a viable strategy.

Biobanking of human biological material and the principle of noncommercialisation of the human body and its parts.

The prohibition of commercialisation of the human body and its parts is not applied consistently and suffers from many exceptions in the human biological material (HBM) market. Examples include the possibility of patenting certain HBM-derived products and their commercial marketing or payments for blood donations. Thus, the current practice of marketing HBM-derived products makes the altruistic donor most vulnerable to exploitation while being deprived of benefits. There seem to be two ways to improve this state of affairs. The first is to apply consistently the prohibition of commercialisation of the body and its parts to commercially marketed tissue and cell products as well. This would require limiting the possibility of financial gain associated with the processing, distribution and sale of HBM-based products. Such a solution, however, does not seem to gain wide acceptance or have a chance of implementation in the near future. Therefore, introducing more transparent rules and greater donor empowerment seems more reasonable by exempting HBM from the ban on commercialisation under certain conditions and with clear limitations.

2,1,3-Benzothiadiazole Small Donor Molecules: A DFT Study, Synthesis, and Optoelectronic Properties.

We herein report the design and synthesis of small-donor molecules, 2,1,3-benzothiadiazole derivatives (2a-d), by Stille or Suzuki reaction. The synthesized compounds were characterized by spectroscopic and electrochemical methods. The compounds 2a-d absorb the light in a wide range (the UV-green/yellow light (2c)) and emit from green to red/near IR light (2c). Furthermore, these compounds show a narrow energy gap (1.75-2.38 eV), and high Ea values increasing for polymers, which prove their electron-donating nature and semiconductor properties. The measurements were enhanced by theoretical modeling.

Conducting Silicone-Based Polymers and Their Application.

Over the past two decades, both fundamental and applied research in conducting polymers have grown rapidly. Conducting polymers (CPs) are unique due to their ease of synthesis, environmental stability, and simple doping/dedoping chemistry. Electrically conductive silicone polymers are the current state-of-the-art for, e.g., optoelectronic materials. The combination of inorganic elements and organic polymers leads to a highly electrically conductive composite with improved thermal stability. Silicone-based materials have a set of extremely interesting properties, i.e., very low surface energy, excellent gas and moisture permeability, good heat stability, low-temperature flexibility, and biocompatibility. The most effective parameters constructing the physical properties of CPs are conjugation length, degree of crystallinity, and intra- and inter-chain interactions. Conducting polymers, owing to their ease of synthesis, remarkable environmental stability, and high conductivity in the doped form, have remained thoroughly studied due to their varied applications in fields like biological activity, drug release systems, rechargeable batteries, and sensors. For this reason, this review provides an overview of organosilicon polymers that have been reported over the past two decades.

Enzymatic Platforms for Sensitive Neurotransmitter Detection.

A convenient electrochemical sensing pathway was investigated for neurotransmitter detection based on newly synthesized silole derivatives and laccase/horseradish-peroxidase-modified platinum (Pt)/gold (Au) electrodes. The miniature neurotransmitter's biosensors were designed and constructed via the immobilization of laccase in an electroactive layer of the Pt electrode coated with poly(2,6-bis(3,4-ethylenedioxythiophene)-4-methyl-4-octyl-dithienosilole) and laccase for serotonin (5-HT) detection, and a Au electrode modified with the electroconducting polymer poly(2,6-bis(selenophen-2-yl)-4-methyl-4-octyl-dithienosilole), along with horseradish peroxidase (HRP), for dopamine (DA) monitoring. These sensing arrangements utilized the catalytic oxidation of neurotransmitters to reactive quinone derivatives (the oxidation process was provided in the enzymes' presence). Under the optimized conditions, the analytical performance demonstrated a convenient degree of sensitivity: 0.0369 and 0.0256 µA mM-1 cm-2, selectivity in a broad linear range (0.1-200) × 10-6 M) with detection limits of ≈48 and ≈73 nM (for the serotonin and dopamine biosensors, respectively). Moreover, the method was successfully applied for neurotransmitter determination in the presence of interfering compounds (ascorbic acid, L-cysteine, and uric acid).

Synthesis and Properties of New Dithienosilole Derivatives as Luminescent Materials.

Three new organosilicon compounds based on dithienosilole (DTSi) were synthesized in good yields. We report the optical and electrochemical properties of the resulting derivatives. We find that these compounds absorb the light in the ultraviolet and blue light range, and they exhibit luminescence in almost the entire range of visible light. After electropolymerization were significantly lowered, the values of the energy gap (even 1.51 eV for P2) and the ionization potential of the polymers were compared to monomers. Optoelectronic properties of the obtained compounds suggest that these derivatives of DTSi may be good candidates as the emissive layers in white organic light-emitting diodes (WOLEDs), which would reduce the amount of layers.

Fibronectin-, vitronectin- and laminin-binding proteins at the cell walls of Candida parapsilosis and Candida tropicalis pathogenic yeasts.

BACKGROUND: Candida parapsilosis and C. tropicalis increasingly compete with C. albicans-the most common fungal pathogen in humans-as causative agents of severe candidiasis in immunocompromised patients. In contrast to C. albicans, the pathogenic mechanisms of these two non-albicans Candida species are poorly understood. Adhesion of Candida yeast to host cells and the extracellular matrix is critical for fungal invasion of hosts. METHODS: The fungal proteins involved in interactions with extracellular matrix proteins were isolated from mixtures of ß-1,3-glucanase- or ß-1,6-glucanase-extractable cell wall-associated proteins by use of affinity chromatography and chemical cross-linking methods, and were further identified by liquid chromatography-coupled tandem mass spectrometry. RESULTS: In the present study, we characterized the binding of three major extracellular matrix proteins--fibronectin, vitronectin and laminin--to C. parapsilosis and C. tropicalis pseudohyphae. The major individual compounds of the fungal cell wall that bound fibronectin, vitronectin and laminin were found to comprise two groups: (1) true cell wall components similar to C. albicans adhesins from the Als, Hwp and Iff/Hyr families; and (2) atypical (cytoplasm-derived) surface-exposed proteins, including malate synthase, glucose-6-phosphate isomerase, 6-phosphogluconate dehydrogenase, enolase, fructose-1,6-bisphosphatase, transketolase, transaldolase and elongation factor 2. DISCUSSION: The adhesive abilities of two investigated non-albicans Candida species toward extracellular matrix proteins were comparable to those of C. albicans suggesting an important role of this particular virulence attribute in the pathogenesis of infections caused by C. tropicalis and C. parapsilosis. CONCLUSIONS: Our results reveal new insight into host-pathogen interactions during infections by two important, recently emerging, fungal pathogens.

International scope of biomedical research ethics review.

Many countries consider long-term implications for society.

The European health data space: Too big to succeed?

In May 2022, the European Commission issued the Proposal for a Regulation on the European Health Data Space (EHDS), with the aims of granting citizens increased access to and control of their (electronic) health data across the EU, and facilitating health data re-use for research, innovation, and policymaking. As the first in a series of European domain-specific "data spaces", the EHDS is a high-stakes development that will transform health data governance in the EU region. As an international consortium of experts from health policy, law, ethics and the social sciences, we are concerned that the EHDS Proposal will detract from, rather than lead to the achievement of, its stated aims. We are in no doubt on the benefits of using health data for secondary purposes, and we appreciate attempts to facilitate such uses across borders in a carefully curated manner. Based on the current draft Regulation, however, the EHDS risks undermining rather than enhancing patient control over data; hindering rather than facilitating the work of health professionals and researchers; and eroding rather than increasing the public value generated through health data sharing. Therefore, significant adjustments are needed if the EHDS is to realize its promised benefits. Besides analyzing the implications for key groups and European societies at large who will be affected by the implementation of the EHDS, this contribution advances targeted policy recommendations to address the identified shortcomings of the EHDS Proposal.

Perylene-Based Chromophore as a Versatile Dye for Light Amplification.

One of the challenges for modern optoelectronics is to find versatile, easily adaptable components for novel laser-based technologies. A very attractive perylene-derivative chromophore in different organic matrices for high-performance light amplification is discussed and outlined. Our approach demonstrates the outstandingly compatible laser dye and a viable strategy to provide an effective optical gain for stimulated emission enhancement. Through structural control, we produce simple optical devices embedded in organic matrices, such as poly(methyl methacrylate), nematic liquid crystalline (NLC) mixture, and a hybrid emulsion system (poly(vinyl alcohol) PVA + NLC mesophase). Importantly, we investigate and compare the spectroscopy of differently constructed organic systems in terms of stimulated-emission thresholds and light amplification process efficiency. Moreover, we report the effects of tunability for LC cells by an applied external electric field stimulus. Future directions of laser systems are outlined with an emphasis on the role of the perylene derivative. The studies meet current challenges in the field of modern organic technologies dedicated to various optoelectronic systems, including touch screens, displays, and Li-Fi networks.

Recommendations for Creating Codes of Conduct for Processing Personal Data in Biobanking Based on the GDPR art.40.

Personal data protection has become a fundamental normative challenge for biobankers and scientists researching human biological samples and associated data. The General Data Protection Regulation (GDPR) harmonises the law on protecting personal data throughout Europe and allows developing codes of conduct for processing personal data based on GDPR art. 40. Codes of conduct are a soft law measure to create protective standards for data processing adapted to the specific area, among others, to biobanking of human biological material. Challenges in this area were noticed by the European Data Protection Supervisor on data protection and Biobanking and BioMolecular Resources Research Infrastructure-European Research Infrastructure Consortium (BBMRI.ERIC). They concern mainly the specification of the definitions of the GDPR and the determination of the appropriate legal basis for data processing, particularly for transferring data to other European countries. Recommendations indicated in the article, which are based on the GDPR, guidelines published by the authority and expert bodies, and our experiences regarding the creation of the Polish code of conduct, should help develop how a code of conduct for processing personal data in biobanks should be developed.

Correction: Electrochemical biosensor for detection of 17ß-estradiol using semi-conducting polymer and horseradish peroxidase.

[This corrects the article DOI: 10.1039/C9RA09902F.].

Electrochemical biosensor for detection of 17ß-estradiol using semi-conducting polymer and horseradish peroxidase.

A convenient electrochemical sensing pathway for 17ß-estradiol detection was investigated. The system is based on a conducting polymer and horseradish peroxidase (HRP) modified platinum (Pt) electrode. The miniature estradiol biosensor was developed and constructed through the immobilization of HRP in an electroactive surface of the electrode covered with electroconducting polymer - poly(4,7-bis(5-(3,4-ethylenedioxythiophene)thiophen-2-yl)benzothiadiazole). The detection strategy is based on the fact that 17ß-estradiol (E2) and pyrocatechol (H2Q) are co-substrates for the HRP enzyme. HRP, which does not react with E2, in the presence of H2O2 catalyses the oxidation of H2Q to o-benzoquinone (Q). With the optimized conditions, such constructed biosensing system demonstrated a convenient level of sensitivity, selectivity in a broad linear range - 0.1 to 200 µM with a detection limit of 105 nM. Furthermore, the method was successfully applied for hormone detection in the presence of potential interfering compounds (ascorbic acid, estriol, estrone, uric acid and cholesterol).

Functional Polymers Structures for (Bio)Sensing Application-A Review.

In this review we present polymeric materials for (bio)sensor technology development. We focused on conductive polymers (conjugated microporous polymer, polymer gels), composites, molecularly imprinted polymers and their influence on the design and fabrication of bio(sensors), which in the future could act as lab-on-a-chip (LOC) devices. LOC instruments enable us to perform a wide range of analysis away from the stationary laboratory. Characterized polymeric species represent promising candidates in biosensor or sensor technology for LOC development, not only for manufacturing these devices, but also as a surface for biologically active materials' immobilization. The presence of biological compounds can improve the sensitivity and selectivity of analytical tools, which in the case of medical diagnostics is extremely important. The described materials are biocompatible, cost-effective, flexible and are an excellent platform for the anchoring of specific compounds.

Impaired plasminogen binding in patients with venous thromboembolism: Association with protein carbonylation.

INTRODUCTION: Venous thromboembolism (VTE) is associated with hypofibrinolysis. Its mechanisms are poorly understood. We investigated plasminogen-fibrin interaction and its association with fibrinolytic capacity and protein oxidation/carbonylation in VTE patients. MATERIALS AND METHODS: Plasma-purified plasminogen conversion to plasmin and surface plasmon resonance employed for plasminogen-fibrin interactions were individually evaluated in all healthy controls and non-anticoagulated patients following VTE, 10-23months since the event. We also assessed plasma fibrin clot permeability (Ks), clot lysis time (LT), activators and inhibitors of fibrinolysis together with oxidation/carbonylation markers. RESULTS: VTE patients had impaired plasminogen binding to fibrin (apparent Kd, +290%, p=0.002), reduced rate of plasmin generation (-4.7%, p=0.001), and longer LT (+18.6%, p<0.001) compared with controls. Fibrinogen and Ks were similar in both groups. Apparent Kd correlated with LT (r=0.43, p=0.037), tissue plasminogen activator-plasminogen activator inhibitor 1 (tPA-PAI-1) complexes (r=0.63, p=0.012), and active PAI-1 (r=0.49, p=0.03). Compared with controls, VTE patients had higher thiobarbituric acid reactive substances (TBARS), total protein carbonyl content (PC), and lower total antioxidant capacity (all p<0.001), that all were associated with LT (r=0.61, r=0.56, and r=-0.47, respectively, all p<0.05). Impaired plasminogen binding to fibrin reflected by apparent Kd positively correlated with TBARS (r=0.48, p=0.032) and PC (r=0.54, p=0.013) in the whole group. CONCLUSIONS: Plasminogen-fibrin interactions are altered in young and middle-aged VTE patients, without known thrombophilias, except increased factor VIII. The mechanisms underlying these phenomena remain to be established.

Binding of human plasminogen and high-molecular-mass kininogen by cell surface-exposed proteins of Candida parapsilosis.

Pathogenic microbes can recruit to their cell surface human proteins that are components of important proteolytic cascades involved in coagulation, fibrinolysis and innate immune response. Once located at the bacterial or fungal surface, such deployed proteins might be utilized by pathogens to facilitate invasion and dissemination within the host organism by interfering with functionality of these systems or by exploiting specific activity of the bound enzymes. Aim of the study presented here was to characterize this phenomenon in Candida parapsilosis (Ashford) Langeron et Talice - an important causative agent of systemic fungal infections (candidiases and candidemias) in humans. We have investigated the interactions of fungal surface-exposed proteins with plasminogen (HPG) and high-molecular-mass kininogen (HK) - the crucial components of human fibrinolytic system and proinflammatory/procoagulant contact-activated kinin-forming system, respectively. After confirming ability of the fungal surface-exposed proteins to bind HPG and HK, four of them - two agglutinin-like sequence (Als) proteins CPAR2_404780 and CPAR2_404800, a heat shock protein Ssa2 and a moonlighting protein 6-phosphogluconate dehydrogenase 1 - were purified using ion-exchange chromatography, gel filtration and chromatofocusing. Then, their affinities to HPG and HK were characterized with surface plasmon resonance measurements. The determined dissociation constants for the investigated protein-protein complexes were within a 10-7 M order for the HPG binding and in a range of 10-8-10-9 M for the HK binding. Detailed characterization of adsorption of these two important plasma proteins on the fungal cell surface may help to increase our understanding of molecular mechanisms of C. parapsilosis-dependent candidiasis.

Interaction of human fibronectin with Candida glabrata epithelial adhesin 6 (Epa6).

Adherence of pathogens to extracellular matrix proteins and host cells is one of the essential steps in the microbial colonization of the human organism. The adhesion of C. glabrata, i.e. the second major causative agent of human disseminated candidiases after C. albicans, to the host epithelium mainly engages specific fungal cell wall proteins - epithelial adhesins (Epa) - in particular, Epa1, Epa6 and Epa7. The aim of the present study was to identify the major Epa protein involved in the interactions with the human extracellular matrix protein - fibronectin - and to present the kinetic and thermodynamic characteristics of these interactions. A relatively novel gel-free approach, i.e. the "cell surface shaving" that consists in short treatment of fungal cells with trypsin was employed to identify the C. glabrata surfaceome. Epa6 was purified, and the isolated protein was characterized in terms of its affinity to human fibronectin using a microplate ligand-binding assay and surface plasmon resonance measurements. The dissociation constants for the binding of Epa6 to fibronectin were determined to range between 9.03 × 10(-9) M and 7.22 × 10(-8) M, depending on the method used (surface plasmon resonance measurements versus the microplate ligand-binding assay, respectively). The identified fungal pathogen-human host protein-protein interactions might become a potential target for novel anticandidal therapeutic approaches.

Characterization of the interactions between human high-molecular-mass kininogen and cell wall proteins of pathogenic yeasts Candida tropicalis.

Candida tropicalis is one of the most frequent causes of serious disseminated candidiasis in human patients infected by non-albicans Candida species, but still relatively little is known about its virulence mechanisms. In our current study, the interactions between the cell surface of this species and a multifunctional human protein - high-molecular-mass kininogen (HK), an important component of the plasma contact system involved in the development of the inflammatory state - were characterized at the molecular level. The quick release of biologically active kinins from candidal cell wall-adsorbed HK was presented and the HK-binding ability was assigned to several cell wall-associated proteins. The predicted hyphally regulated cell wall protein (Hyr) and some housekeeping enzymes exposed at the cell surface (known as "moonlighting proteins") were found to be the major HK binders. Accordingly, after purification of selected proteins, the dissociation constants of the complexes of HK with Hyr, enolase, and phosphoglycerate mutase were determined using surface plasmon resonance measurements, yielding the values of 2.20 × 10(-7) M, 1.42 × 10(-7) M, and 5.81 × 10(-7) M, respectively. Therefore, in this work, for the first time, the interactions between C. tropicalis cell wall proteins and HK were characterized in molecular terms. Our findings may be useful for designing more effective prevention and treatment approaches against infections caused by this dangerous fungal pathogen.

Surfaceome of pathogenic yeasts, Candida parapsilosis and Candida tropicalis, revealed with the use of cell surface shaving method and shotgun proteomic approach.

In the course of infections caused by pathogenic yeasts from the genus Candida, the fungal cell surface is the first line of contact with the human host. As the surface-exposed proteins are the key players in these interactions, their identification can significantly contribute to discovering the mechanisms of pathogenesis of two emerging pathogens from this genus, C. parapsilosis and C. tropicalis. Therefore, the aim of the present study was to identify the cell wall-attached proteins of these two species with the use of cell surface shaving and a shotgun proteomic approach. Different morphological forms of C. parapsilosis and C. tropicalis cells obtained after growth under various conditions were subjected to this treatment. This allowed to indicate the most abundant cell surface proteins on the basis of the normalized spectral abundance factors. In case of yeast-like forms these were, among others, proteins similar to a chitinase, glyceraldehyde-3-phosphate dehydrogenase and an inducible acid phosphatase for C. parapsilosis, and a constitutive acid phosphatase, pyruvate decarboxylase and glyceraldehyde-3-phosphate dehydrogenase for C. tropicalis. In case of pseudohyphal forms, proteins similar to a cell surface mannoprotein Mp65, chitinase and glycosylphosphatidylinositol-anchored transglycosylase Crh11 were identified at the cell surface of C. parapsilosis. The Rbt1 cell wall protein, a hyphally regulated cell wall protein and proteins from agglutinin-like sequence protein family were found as the most abundant on C. tropicalis pseudohyphae. Apart from the abovementioned proteins, several additional covalently bound and atypical cell wall proteins were also identified. These results extend the current knowledge regarding the molecular basis of virulence of these two non-albicans Candida species.