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Suction feeding in fishes is characterized by rapid cranial movements, but extant lungfishes (Sarcopterygii: Dipnoi) exhibit a reduced number and mobility of cranial bones relative to actinopterygian fishes. Despite fusion of cranial elements, lungfishes are proficient at suction feeding, though the impacts of novel cranial morphology and reduced cranial kinesis on feeding remain poorly understood. We used X-ray reconstruction of moving morphology (XROMM) to study the kinematics of seven mobile elements (neurocranium, upper jaw, lower jaw, tongue, ceratohyal, clavicle, and cranial rib) and two muscles (costoclavicular portion of the hypaxialis and rectus cervicis) during the feeding strikes of West African lungfish (Protopterus annectens). We found that feeding by P. annectens on non-evasive prey is relatively slow, with a mean time to peak gape of 273 ms. Lower jaw depression and clavicular rotation were hinge-like, with one degree of freedom, but the ceratohyals rotated in a complex motion involving depression and long-axis rotation. We quantified the relative contributions to oral cavity volume change (RCVC) and found that oral cavity expansion is created primarily by ceratohyal and clavicle motion. P. annectens suction feeds relatively slowly but successfully through muscle shortening of hypaxial and rectus cervicis muscles contributing to hyoid mobility.

A guiding principle in self-assembly is that, for high production yield, nucleation of structures must be significantly slower than their growth. However, details of the mechanism that impedes nucleation are broadly considered irrelevant. Here, we analyze self-assembly into finite-sized target structures employing mathematical modeling. We investigate two key scenarios to delay nucleation: (i) by introducing a slow activation step for the assembling constituents and, (ii) by decreasing the dimerization rate. These scenarios have widely different characteristics. While the dimerization scenario exhibits robust behavior, the activation scenario is highly sensitive to demographic fluctuations. These demographic fluctuations ultimately disfavor growth compared to nucleation and can suppress yield completely. The occurrence of this stochastic yield catastrophe does not depend on model details but is generic as soon as number fluctuations between constituents are taken into account. On a broader perspective, our results reveal that stochasticity is an important limiting factor for self-assembly and that the specific implementation of the nucleation process plays a significant role in determining the yield.

Glasses with composition of GexSb40-xSe60 (x= 40, 35, 32, 27, 20, 15 at. %) have been synthesized. Neutron and X-ray diffraction techniques were used to study the atomic glassy structure, and Reverse Monte Carlo (RMC) simulations were applied to model the 3-dimensional atomic configurations and thorough mapping of the atomic parameters, such as first and second neighbour distances, coordination numbers, and bond-angle distributions. The results are explained with formation of GeSe4 and SbSe3 structural units, which correlate with the Ge/Sb ratio. For all the studied compositions, the Ge-Se, Sb-Se, Ge-Ge, and Se-Se bonds are significant. RMC simulations reveal the presence of Ge-Sb and Sb-Sb bonds, being dependent on Ge/Sb ratio. All atomic compositions satisfy formal valence requirements, i.e., Ge is fourfold coordinated, Sb is threefold coordinated, and Se is twofold coordinated. By increasing the Sb content, both the Se-Ge-Se bonds angle of 107±3° and Se-Sb-Se bonds angle of 118±3° decrease, respectively, indicating distortion of the structural units. Far infrared Fourier Transform spectroscopic measurements conducted in the range of 50-450 cm-1 at oblique (75°) incidence radiation have revealed clear dependences of the IR band’s shift and intensity on the glassy composition, showing features around x=27 at.% supporting the topological phase transition to a stable rigid network consisting mainly of SbSe3 pyramidal and GeSe4 tetrahedral clusters. These results are in agreement with the Reverse Monte Carlo models, which define the Ge and Sb environment.

We present comparative studies of sol-gel ITO multilayered films undoped and doped with Nb or Zn (4 at.%). The films were obtained by successive depositions of five layers using the dip-coating sol-gel method on microscopic glass, SiO 2 /glass, and Si substrates. The influence of the type of substrates and dopant atoms on the structure and optical properties of the sol-gel ITO thin films is examined and discussed in detail. XRD patterns of these layers showed a polycrystalline structure with an average crystallite size of <11 nm. Raman spectroscopy confirmed the chemical bonding of dopants with oxygen and showed the absence of crystallized Nb(Zn)-oxide particles, indicated by the XRD pattern. Spectroscopic Ellipsometry and AFM imaging revealed a clear dependence of the optical parameters and surface morphology of the ITO and ITO:Nb(Zn) thin films on the type of substrates and dopants. The analysis of the current-voltage and capacitance-voltage characteristics of the Al/ITO/Si structures revealed the presence of charge carrier traps in the ITO bulk and the ITO-Si interface. The densities of these traps are obtained and the character of the current transport mechanism is established.

Multilayered TiO 2 films doped either with Niobium or Vanadium (1.2 at. %) were deposited by the sol-gel dip coating method on c-Si and glass substrates. The films on glass substrates were tested for CO sensing and photocatalytic degradation of methylene blue. X-ray diffraction data analysis showed that all the TiO 2 :Nb(V) films were nanocrystalline in the anatase phase, with a uniform and compact microstructure and a homogeneous superficial structure of small grains with diameters in the range of 13-19 nm. For the electrical characterization, the TiO 2 :Nb(V) films were incorporated in Metal-Insulator-Semiconductor (MIS) structures. The specific resistivity is of the order of 10 4 Ωcm and its value decreases with increasing the electrical field, which testifies to the injection of electrons into these layers. From the analysis of the current-voltage curves taken at different temperature- and frequency-dependent capacitance-voltage and conductance-voltage characteristics, the density and parameters of deep levels in these TiO 2 films are evaluated and the electron charge transport mechanism is established. It was shown that the current in these TiO 2 :Nb(V)-Si MIS structures is mainly carried out by inter-trap tunneling via deep levels energetically distributed in the TiO 2 bandgap. Testing these sol-gel TiO 2 :Nb(V) layers for gas sensing and photocatalytic capabilities proved that they could serve such purposes. In particular, the results of the V-doped sol-gel TiO 2 film confirm its CO detection capability, which is rarely reported in the literature. For the photodegradation of methylene blue, the Nb-doped TiO 2 samples were superior, with nearly double the photocatalytic efficiency of undoped TiO 2 .

For many years, TiO 2 -based materials and improving their properties in order to expand their application areas have been the focus of numerous research groups. Various innovative approaches have been proposed to improve the photocatalytic and gas-sensing properties of TiO 2 nanostructures. In this review, we aim to synthesize the available information in the literature, paying special attention to the sol-gel technology, which is one of the most frequently used methods for TiO 2 synthesis. The influence of dopants on the structural, morphological, optical, and electrical properties of TiO 2 and the way to modify them in a controlled manner are briefly discussed. The role of shallow and/or deep energy levels within the TiO 2 bandgap in the electron transport behavior of doped TiO 2 is emphasized. Selected research on photocatalytic applications in water disinfection, wastewater treatment, and self-sterilizing coatings that contribute to improving the quality of human life and environmental preservation is highlighted. A survey of biosensors that are closely related to medical applications such as cancer detection, implantology, and osteogenesis is also provided. Finally, the pressing problems that need to be solved in view of the future development of TiO 2 -based nanostructures are listed.

Kaposi's sarcoma-associated herpesvirus (KSHV) can establish latent lifelong infections in infected individuals. During viral latency, the latency-associated nuclear antigen (LANA) mediates the replication of the latent viral genome in dividing cells and tethers them to mitotic chromosomes, thus ensuring their partitioning into daughter cells during mitosis. This study aims to inhibit Kaposi's sarcoma-associated herpesvirus (KSHV) latent replication by targeting the LANA-DNA interaction using small molecular entities. Drawing from first-generation inhibitors and using growth vectors identified through STD-NMR, we expanded these compounds using Suzuki-Miyaura cross-coupling. This led to a deeper understanding of SAR achieved by microscale thermophoresis (MST) measurements and cell-free tests via electrophoretic mobility shift assays (EMSA). Our most potent compounds successfully inhibit LANA-mediated replication in cell-based assays and demonstrate favorable in vitro ADMET-profiles, including suitable metabolic stability, Caco-2 permeability, and cytotoxicity. These compounds could serve as qualified leads for the future refinement of small molecule inhibitors of KSHV latent replication.

Wastewater treatment targeting reuse may limit water scarcity. Photocatalysis is an advanced oxidation process that may be employed in the removal of traces of organic pollutants, where the material choice is important. Titanium dioxide (TiO 2 ) is a highly efficient photocatalyst with good aqueous stability. TiO 2 powder has a high surface area, thus allowing good pollutant adsorption, but it is difficult to filter for reuse. Thin films have a significantly lower surface area but are easier to regenerate and reuse. In this paper, we report on obtaining sol-gel TiO 2 thin films on spherical beads (2 mm diameter) with high surface area and easy recovery from wastewater. The complex influence of the substrate morphology (etched up to 48 h in concentrated H 2 SO 4 ), of the sol dilution with ethanol (1:0 or 1:1), and the number of layers (1 or 2) on the structure, morphology, chemical composition, and photocatalytic performance of the TiO 2 thin films is investigated. Etching the substrate for 2 h in H 2 SO 4 leads to uniform, smooth surfaces on which crystalline, homogeneous TiO 2 thin films are grown. Films deposited using an undiluted sol are stable in water, with some surface reorganization of the TiO 2 aggregates occurring, while the films obtained using diluted sol are partially washed out. By increasing the film thickness through the deposition of a second layer, the roughness increases (from ~50 nm to ~100 nm), but this increase is not high enough to promote higher adsorption or overall photocatalytic efficiency in methylene blue photodegradation (both about 40% after 8 h of UV-Vis irradiation at 55 W/m 2 ). The most promising thin film, deposited on spherical bead substrates (etched for 2 h in H 2 SO 4 ) using the undiluted sol, with one layer, is highly crystalline, uniform, water-stable, and proves to have good photocatalytic activity.

Fecal glucocorticoid metabolite (FGM) concentrations, activity, and personality were assessed for 35 fennec foxes ( Vulpes zerda ) to determine whether animals managed as ambassadors differed from exhibit or off-exhibit animals. A FGM assay, pedometer, and personality assessment tool were validated. Then, fecal samples and movement data were collected during winter and summer periods. Handling was recorded, and the personality of each fox was evaluated. Generalized linear mixed models assessed the relationships between FGM concentrations, activity, personality, handling, sex, season, rearing type, and role. FGM concentrations did not differ in relation to role or handling. Foxes were most active at night; the time of peak activity did not vary with role or handling. Foxes were more active in winter; males were more active than females, and ambassador foxes were more active than off-exhibit animals. Hand-reared foxes were more sociable, and, at one institution, ambassador foxes were more sociable than foxes in other roles. These results suggest that management for ambassador programs is not associated with changes in glucocorticoid production or circadian patterns but may increase activity and be associated with greater sociability.

This review addresses the importance of Zn for obtaining multifunctional materials with interesting properties by following certain preparation strategies: choosing the appropriate synthesis route, doping and co-doping of ZnO films to achieve conductive oxide materials with p- or n-type conductivity, and finally adding polymers in the oxide systems for piezoelectricity enhancement. We mainly followed the results of studies of the last ten years through chemical routes, especially by sol-gel and hydrothermal synthesis. Zinc is an essential element that has a special importance for developing multifunctional materials with various applications. ZnO can be used for the deposition of thin films or for obtaining mixed layers by combining ZnO with other oxides (ZnO-SnO 2 , ZnO-CuO). Also, composite films can be achieved by mixing ZnO with polymers. It can be doped with metals (Li, Na, Mg, Al) or non-metals (B, N, P). Zn is easily incorporated in a matrix and therefore it can be used as a dopant for other oxidic materials, such as: ITO, CuO, BiFeO 3, and NiO. ZnO can be very useful as a seed layer, for good adherence of the main layer to the substrate, generating nucleation sites for nanowires growth. Thanks to its interesting properties, ZnO is a material with multiple applications in various fields: sensing technology, piezoelectric devices, transparent conductive oxides, solar cells, and photoluminescence applications. Its versatility is the main message of this review.

The opioid epidemic has impacted over 10 million Americans in 2019. Opioids, like morphine, bind non-selectively in both peripheral tissue, leading to effective pain relief, and central tissue, resulting in dangerous side effects and addiction. The inflamed conditions of injured tissues have a lower pH (pH = 6-6.5) environment than healthy tissue (pH = 7.4). We aim to design a morphine derivative that binds selectively within inflamed tissue using molecular extension and dissection techniques. Morphine binds to the μ-opioid receptor (MOR) when the biochemically active amine group is protonated. Fluorination of a β-carbon from the tertiary amine group led to a reduced pKa of the derivative through induction. Through a decrease in the pKa, protonation is still statistically favored in lower pH environments of inflamed tissue but primarily deprotonated in healthy tissue. The cyclohexenol and N-methyl-piperidine rings of morphine are removed to increase conformational flexibility when binding while still maintaining the interactions required for analgesia. Electronic structure calculations were performed with Gaussian16 using the Keck Computational Research Cluster at Chapman University to determine the pKa. The theoretical pKa values are determined at the M06-2X(SMD)/aug-cc-pVDZ level of theory to calculate the ΔG°aq values for the amine deprotonation reactions. Fluoromorphine β-C2 was designed computationally and modeled within the MOR using Maestro: Schrödinger. This derivative exhibits a pKa reduction and enhanced ligand-protein interactions within the MOR. β-fluorination decreased the overall pKa values of the morphine derivatives (pKa: 6.1-7.83) relative to morphine, reducing binding within healthy, central tissue., (© 2023 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

Background: The United Nations calculates there were 703 million adults 65 years and older globally as of 2019 with this number projected to double by 2050. A significant number of older adults live with comorbid health conditions, making the role of a nurse in long-term care (LTC) complex. Our objective was to identify the challenges, facilitators, workload, professional development and clinical environment issues that influence nurses and nursing students to seek work and continue to work in LTC settings., Methods: Eligibility criteria included being a nurse in a LTC setting and research with a substantial qualitative component. Multiple databases (including Medline and CINAHL) were searched between 2013 and 2019 along with grey literature. Covidence was used to organise a team of 10 into a paired review of titles and abstracts to the final full text screening, extraction and appraisal with the CASP Qualitative Studies Checklist. Analysis involved a thematic synthesis approach. The Enhancing Transparency in Reporting the Synthesis of Qualitative Research (ENTREQ) checklist informed the writing of the review., Results: The search resulted in 18 articles and dissertations. Areas investigated included recruitment, resilience, employment and retention, how nurses perceived their professional work, rewards and difficulties, supervision, student preceptorship and career aspiration, nurses' perceptions of occupational status, along with leadership, education and development needs, and intentions to manage resident deteriorating health. The five themes were (1) perspectives of nursing influenced by the organisation, (2) pride in, and capacity to build relationships, (3) stretching beyond the technical skills, (4) autonomy, and (5) taking on the challenge of societal perceptions., Discussion: This review revealed what is required to recruit nursing students to careers in LTC and retain nurses. To be explored is how staff can work to their full scope of practice and the resultant impact on resident care, including how to maximise a meaningful life for residents and their families., Registration: National Institute for Health Research UK (Prospero ID: CRD42019125214)., (© 2021 John Wiley & Sons Ltd.)

ZnO and Al-doped ZnO (AZO) thin films were prepared using the sol-gel method and deposited on a Silicon (Si(100)) substrate using the dipping technique. The structure, morphology, thickness, optical constants in the spectral range 300-1700 nm, bandgap (E g ) and photoluminescence (PL) properties of the films were analyzed using X-ray diffractometry (XRD), X-ray fluorescence (XRF), atomic force microscopy (AFM), scanning electron microscopy (SEM), spectroscopic ellipsometry (SE), Raman analysis and PL spectroscopy. The results of the structure and morphology analyses showed that the thin films are polycrystalline with a hexagonal wurtzite structure, as well as continuous and homogeneous. The PL background and broader peaks observable in the Raman spectra of the AZO film and the slight increase in the optical band gap of the AZO thin film, compared to undoped ZnO, highlight the effect of defects introduced into the ZnO lattice and an increase in the charge carrier density in the AZO film. The PL emission spectra of the AZO thin film showed a strong UV line corresponding to near-band-edge ZnO emission along with weak green and red emission bands due to deep-level defects, attributed to the oxygen-occupied zinc vacancies (O Zn lattice defects).

Detection of greenhouse gases is essential because harmful gases in the air diffuse rapidly over large areas in a short period of time, causing air pollution that will induce climate change with catastrophic consequences over time. Among the materials with favorable morphologies for gas detection (nanofibers, nanorods, nanosheets), large specific surfaces, high sensitivity and low production costs, we chose nanostructured porous films of In 2 O 3 obtained by the sol-gel method, deposited on alumina transducers, with gold (Au) interdigitated electrodes (IDE) and platinum (Pt) heating circuits. Sensitive films contained 10 deposited layers, involving intermediate and final thermal treatments to stabilize the sensitive film. The fabricated sensor was characterized using AFM, SEM, EDX and XRD. The film morphology is complex, containing fibrillar formations and some quasi-spherical conglomerates. The deposited sensitive films are rough, thus favoring gas adsorption. Ozone sensing tests were performed at different temperatures. The highest response of the ozone sensor was recorded at room temperature, considered to be the working temperature for this specific sensor.

Methane is a colorless/odorless major greenhouse effect gas, which can explode when it accumulates at concentrations above 50,000 ppm. Its detection cannot be performed without specialized equipment, namely sensing devices. A series of MOX sensors ( chemiresistors type), with CoO and CuO sensitive films were obtained using an eco-friendly and low-cost deposition technique (sol-gel). The sensing films were characterized using AFM and SEM as thin film. The transducers are based on an alumina wafer, with Au or Pt interdigital electrodes (IDE) printed onto the alumina surface. The sensor response was recorded upon sensor exposure to different methane concentrations (target gas) under lab conditions (dried target and carrier gas from gas cylinders), in a constant gas flow, with target gas concentrations in the 5-2000 ppm domain and a direct current (DC) applied to the IDE as sensor operating voltage. Humidity and cross-sensitivity (CO 2 ) measurements were performed, along with sensor stability measurements, to better characterize the obtained sensors. The obtained results emphasize good 3-S sensor parameters (sensitivity, partial selectivity and stability) and also short response time and complete sensor recovery, completed by a low working temperature (220 °C), which are key factors for further development of a new commercial chemiresistor for methane detection.

The aim of the present study was the development of Nb-doped ITO thin films for carbon monoxide (CO) sensing applications. The detection of CO is imperious because of its high toxicity, with long-term exposure having a negative impact on human health. Using a feasible sol-gel method, the doped ITO thin films were prepared at room temperature and deposited onto various substrates (Si, SiO 2 /glass, and glass). The structural, morphological, and optical characterization was performed by the following techniques: X-ray diffractometry (XRD), atomic force microscopy (AFM), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and UV/Vis/NIR spectroscopic ellipsometry (SE). The analysis revealed a crystalline structure and a low surface roughness of the doped ITO-based thin films. XTEM analysis (cross-sectional transmission electron microscopy) showed that the film has crystallites of the order of 5-10 nm and relatively large pores (around 3-5 nm in diameter). A transmittance value of 80% in the visible region and an optical band-gap energy of around 3.7 eV were found for dip-coated ITO/Nb films on SiO 2 /glass and glass supports. The EDX measurements proved the presence of Nb in the ITO film in a molar ratio of 3.7%, close to the intended one (4%). Gas testing measurements were carried out on the ITO undoped and doped thin films deposited on glass substrate. The presence of Nb in the ITO matrix increases the electrical signal and the sensitivity to CO detection, leading to the highest response for 2000 ppm CO concentration at working temperature of 300 °C.

Undoped and Zn-doped ITO (ITO:Zn) multifunctional thin films were successfully synthesized using the sol-gel and dipping method on three different types of substrates (glass, SiO 2 /glass, and Si). The effect of Zn doping on the optoelectronic, microstructural, and gas-sensing properties of the films was investigated using X-ray diffraction (XRD), atomic force microscopy (AFM), scanning electron microscopy (SEM), transmission electron microscopy (TEM), spectroscopic ellipsometry (SE), Raman spectroscopy, Hall effect measurements (HE), and gas testing. The results showed that the optical constants, the transmission, and the carrier numbers were correlated with the substrate type and with the microstructure and the thickness of the films. The Raman study showed the formation of ITO films and the incorporation of Zn in the doped film (ITO:Zn), which was confirmed by EDX analysis. The potential use of the multifunctional sol-gel ITO and ITO:Zn thin films was proven for TCO applications or gas-sensing experiments toward CO 2 . The Nyquist plots and equivalent circuit for fitting the experimental data were provided. The best electrical response of the sensor in CO 2 atmosphere was found at 150 °C, with activation energy of around 0.31 eV.

Both DNA- and RNA-based nanotechnologies are remarkably useful for the engineering of molecular devices in vitro and are applied in a vast collection of applications. Yet, the ability to integrate functional nucleic acid nanostructures in applications outside of the lab requires overcoming their inherent degradation sensitivity and subsequent loss of function. Viruses are minimalistic yet sophisticated supramolecular assemblies, capable of shielding their nucleic acid content in nuclease-rich environments. Inspired by this natural ability, we engineered RNA-virus-like particles (VLPs) nanocarriers (NCs). We showed that the VLPs can function as an exceptional protective shell against nuclease-mediated degradation. We then harnessed biological recognition elements and demonstrated how engineered riboswitch NCs can act as a possible disease-modifying treatment for genetic metabolic disorders. The functional riboswitch is capable of selectively and specifically binding metabolites and preventing their self-assembly process and its downstream effects. When applying the riboswitch nanocarriers to an in vivo yeast model of adenine accumulation and self-assembly, significant inhibition of the sensitivity to adenine feeding was observed. In addition, using an amyloid-specific dye, we proved the riboswitch nanocarriers' ability to reduce the level of intracellular amyloid-like metabolite cytotoxic structures. The potential of this RNA therapeutic technology does not apply only to metabolic disorders, as it can be easily fine-tuned to be applied to other conditions and diseases.

Recently the emissions of volatile organic compounds (VOCs) in the atmosphere have increased dramatically with rapid development of urbanization and industry. This led to a large decline in air quality around the world, which resulted in a heavy impact on human health. Therefore, new/cheap detection devices for VOCs are of high interest. Formaldehyde (FA) is a very toxic VOC, which damages the respiratory system even in the smallest doses and short exposure time. Zinc oxide (ZnO)/nickel oxide (NiO) heterostructures were synthesized using an economical route: firstly, NiO was prepared by liquid exfoliation technique and deposited by dip-coating on alumina ceramic transducers with two interdigital gold (Au) electrodes, followed by low-temperature hydrothermal growth of ZnO. The as-prepared sensors were characterized by atomic force microscopy (AFM), scanning electron microscopy (SEM-EDAX), and X-Ray fluorescence (XRF). The response/recovery of ZnO/NiO heterostructure-based microsensors for formaldehyde was investigated at room temperature, in agreement with modern sensing requirements. The sensor operating voltage was varied between 1.5 and 5.0 V direct current (DC), to achieve the best sensor performance., Competing Interests: Conflict of interestThe authors have no competing interests to declare that are relevant to the content of this article., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Nitrogen-doped ZnO (ZnO:N) thin films, deposited on Si(100) substrates by RF magnetron sputtering in a gas mixture of argon, oxygen, and nitrogen at different ratios followed by Rapid Thermal Annealing (RTA) at 400 °C and 550 °C, were studied in the present work. Raman and photoluminescence spectroscopic analyses showed that introduction of N into the ZnO matrix generated defects related to oxygen and zinc vacancies and interstitials. These defects were deep levels which contributed to the electron transport properties of the ZnO:N films, studied by analyzing the current-voltage characteristics of metal-insulator-semiconductor structures with ZnO:N films, measured at 298 and 77 K. At the appliedtechnological conditions of deposition and subsequent RTA at 400 °C n-type ZnO:N films were formed, while RTA at 550 °C transformed the n-ZnO:N films to p-ZnO:N ones. The charge transport in both types of ZnO:N films was carried out via deep levels in the ZnO energy gap. The density of the deep levels was in the order of 10 19 cm -3 . In the temperature range of 77-298 K, the electron transport mechanism in the ZnO:N films was predominantly intertrap tunneling, but thermally activated hopping also took place.

Although the respiratory tract is the primary site of SARS-CoV-2 infection and the ensuing immunopathology, respiratory immune responses are understudied and urgently needed to understand mechanisms underlying COVID-19 disease pathogenesis. We collected paired longitudinal blood and respiratory tract samples (endotracheal aspirate, sputum or pleural fluid) from hospitalized COVID-19 patients and non-COVID-19 controls. Cellular, humoral and cytokine responses were analysed and correlated with clinical data. SARS-CoV-2-specific IgM, IgG and IgA antibodies were detected using ELISA and multiplex assay in both the respiratory tract and blood of COVID-19 patients, although a higher receptor binding domain (RBD)-specific IgM and IgG seroconversion level was found in respiratory specimens. SARS-CoV-2 neutralization activity in respiratory samples was detected only when high levels of RBD-specific antibodies were present. Strikingly, cytokine/chemokine levels and profiles greatly differed between respiratory samples and plasma, indicating that inflammation needs to be assessed in respiratory specimens for the accurate assessment of SARS-CoV-2 immunopathology. Diverse immune cell subsets were detected in respiratory samples, albeit dominated by neutrophils. Importantly, we also showed that dexamethasone and/or remdesivir treatment did not affect humoral responses in blood of COVID-19 patients. Overall, our study unveils stark differences in innate and adaptive immune responses between respiratory samples and blood and provides important insights into effect of drug therapy on immune responses in COVID-19 patients.

High levels of homocysteine are reported as a risk factor for Alzheimer's disease (AD). Correspondingly, inborn hyperhomocysteinemia is associated with an increased predisposition to the development of dementia in later stages of life. Yet, the mechanistic link between homocysteine accumulation and the pathological neurodegenerative processes is still elusive. Furthermore, despite the clear association between protein aggregation and AD, attempts to develop therapy that specifically targets this process have not been successful. It is envisioned that the failure in the development of efficacious therapeutic intervention may lie in the metabolomic state of affected individuals. We recently demonstrated the ability of metabolites to self-assemble and cross-seed the aggregation of pathological proteins, suggesting a role for metabolite structures in the initiation of neurodegenerative diseases. Here, we provide a report of homocysteine crystal structure and self-assembly into amyloid-like toxic fibrils, their inhibition by polyphenols, and their ability to seed the aggregation of the AD-associated β-amyloid polypeptide. A yeast model of hyperhomocysteinemia indicates a toxic effect, correlated with increased intracellular amyloid staining that could be rescued by polyphenol treatment. Analysis of AD mouse model brain sections indicates the presence of homocysteine assemblies and the interplay between β-amyloid and homocysteine. This work implies a molecular basis for the association between homocysteine accumulation and AD pathology, potentially leading to a paradigm shift in the understanding of AD initial pathological processes., Competing Interests: The authors declare no competing interest.

The development of short-wave infrared (SWIR) photonics based on GeSn alloys is of high technological interest for many application fields, such as the Internet of things or pollution monitoring. The manufacture of crystalline GeSn is a major challenge, mainly because of the low miscibility of Ge and Sn. The use of embedded GeSn nanocrystals (NCs) by magnetron sputtering is a cost-effective and efficient method to relax the growth conditions. We report on the use of GeSn/SiO 2 multilayer deposition as a way to control the NC size and their insulation. The in situ prenucleation of NCs during deposition was followed by ex situ rapid thermal annealing. The nanocrystallization of 20×(11nm&#95;Ge 0.865 Sn 0.135 /1.5nm&#95;SiO 2 ) multilayers leads to formation of GeSn NCs with ∼16% Sn concentration and ∼9 nm size. Formation of GeSn domes that are vertically correlated contributes to the nanocrystallization process. The absorption limit of ∼0.4 eV in SWIR found by ellipsometry is in agreement with the spectral photosensitivity. The ITO/20×(GeSn NC/SiO 2 )/p-Si/Al diodes show a maximum value of the SWIR photosensitivity at a reverse voltage of 0.5 V, with extended sensitivity to wavelengths longer than 2200 nm. The multilayer diodes have higher photocurrent efficiency compared to diodes based on a thick monolayer of GeSn NCs.

The environmental monitoring of Ni is targeted at a threshold limit value of 0.34 μM, as set by the World Health Organization. This sensitivity target can usually only be met by time-consuming and expensive laboratory measurements. There is a need for inexpensive, field-applicable methods, even if they are only used for signaling the necessity of a more accurate laboratory investigation. In this work, bioengineered, protein-based sensing layers were developed for Ni detection in water. Two bacterial Ni-binding flagellin variants were fabricated using genetic engineering, and their applicability as Ni-sensitive biochip coatings was tested. Nanotubes of mutant flagellins were built by in vitro polymerization. A large surface density of the nanotubes on the sensor surface was achieved by covalent immobilization chemistry based on a dithiobis(succimidyl propionate) cross-linking method. The formation and density of the sensing layer was monitored and verified by spectroscopic ellipsometry and atomic force microscopy. Cyclic voltammetry (CV) measurements revealed a Ni sensitivity below 1 μM. It was also shown that, even after two months of storage, the used sensors can be regenerated and reused by rinsing in a 10 mM solution of ethylenediaminetetraacetic acid at room temperature.

HIV can persist in people living with HIV (PLWH) on antiretroviral therapy (ART) in multiple CD4 + T cell subsets, including naive cells, central memory (CM) cells, transitional (TM) cells, and effector memory (EM) cells. Since these cells express different levels of the viral coreceptors CXCR4 and CCR5 on their surface, we sought to determine whether the HIV envelope protein (Env) was genotypically and phenotypically different between CD4 + T cell subsets isolated from PLWH on suppressive ART ( n  = 8). Single genome amplification for the HIV env gene was performed on genomic DNA extracts from different CD4 + T cell subsets. We detected CXCR4-using (X4) strains in five of the eight participants studied, and in these participants, the prevalence of X4 strains was higher in naive CD4 + T cells than in the memory subsets. Conversely, R5 strains were mostly found in the TM and EM populations. Identical sets of env sequences, consistent with clonal expansion of some infected cells, were more frequent in EM cells. These expanded identical sequences could also be detected in multiple CD4 + T cell subsets, suggesting that infected cells can undergo T cell differentiation. These identical sequences largely encoded intact and functional Env proteins. Our results are consistent with a model in which X4 HIV strains infect and potentially establish latency in naive and CM CD4 + T cells through direct infection, in addition to maintenance of the reservoir through differentiation and proliferation of infected cells. IMPORTANCE In people living with HIV (PLWH) on suppressive ART, latent HIV can be found in a diverse range of CD4 + T cells, including quiescent naive and central memory cells that are typically difficult to infect in vitro It is currently unclear how latency is established in these cells in vivo We show that in CD4 + T cells from PLWH on suppressive ART, the use of the coreceptor CXCR4 was prevalent among viruses amplified from naive and central memory CD4 + T cells. Furthermore, we found that expanded numbers of identical viral sequences were most common in the effector memory population, and these identical sequences were also found in multiple different CD4 + T cell subsets. Our results help to shed light on how a range of CD4 + T cell subsets come to harbor HIV DNA, which is one of the major barriers to eradicating the virus from PLWH., (Copyright © 2020 American Society for Microbiology.)

Background: Identifying where human immunodeficiency virus (HIV) persists in people living with HIV and receiving antiretroviral therapy is critical to develop cure strategies. We assessed the relationship of HIV persistence to expression of chemokine receptors and their chemokines in blood (n = 48) and in rectal (n = 20) and lymph node (LN; n = 8) tissue collected from people living with HIV who were receiving suppressive antiretroviral therapy., Methods: Cell-associated integrated HIV DNA, unspliced HIV RNA, and chemokine messenger RNA were quantified by quantitative polymerase chain reaction. Chemokine receptor expression on CD4+ T cells was determined using flow cytometry., Results: Integrated HIV DNA levels in CD4+ T cells, CCR6+CXCR3+ memory CD4+ T-cell frequency, and CCL20 expression (ligand for CCR6) were highest in rectal tissue, where HIV-infected CCR6+ T cells accounted for nearly all infected cells (median, 89.7%). Conversely in LN tissue, CCR6+ T cells were infrequent, and there was a statistically significant association of cell-associated HIV DNA and RNA with CCL19, CCL21, and CXCL13 chemokines., Conclusions: HIV-infected CCR6+ CD4+ T cells accounted for the majority of infected cells in rectal tissue. The different relationships between HIV persistence and T-cell subsets and chemokines in rectal and LN tissue suggest that different tissue-specific strategies may be required to eliminate HIV persistence and that assessment of biomarkers for HIV persistence may not be generalizable between blood and other tissues., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

The extension of the amyloid hypothesis to include non-protein metabolite assemblies invokes a paradigm for the pathology of inborn error of metabolism disorders. However, a direct demonstration of the assembly of metabolite amyloid-like structures has so far been provided only in vitro. Here, we established an in vivo model of adenine self-assembly in yeast, in which toxicity is associated with intracellular accumulation of the metabolite. Using a strain blocked in the enzymatic pathway downstream to adenine, we observed a non-linear dose-dependent growth inhibition. Both the staining with an indicative amyloid dye and anti-adenine assemblies antibodies demonstrated the accumulation of adenine amyloid-like structures, which were eliminated by lowering the supplied adenine levels. Treatment with a polyphenol inhibitor reduced the occurrence of amyloid-like structures while not affecting the dramatic increase in intracellular adenine concentration, resulting in inhibition of cytotoxicity, further supporting the notion that toxicity is triggered by adenine assemblies.

Background: Spermidine administration is linked to increased survival in several animal models., Objective: The aim of this study was to test the potential association between spermidine content in diet and mortality in humans., Design: This prospective community-based cohort study included 829 participants aged 45-84 y, 49.9% of whom were male. Diet was assessed by repeated dietitian-administered validated food-frequency questionnaires (2540 assessments) in 1995, 2000, 2005, and 2010. During follow-up between 1995 and 2015, 341 deaths occurred., Results: All-cause mortality (deaths per 1000 person-years) decreased across thirds of increasing spermidine intake from 40.5 (95% CI: 36.1, 44.7) to 23.7 (95% CI: 20.0, 27.0) and 15.1 (95% CI: 12.6, 17.8), corresponding to an age-, sex- and caloric intake-adjusted 20-y cumulative mortality incidence of 0.48 (95% CI: 0.45, 0.51), 0.41 (95% CI: 0.38, 0.45), and 0.38 (95% CI: 0.34, 0.41), respectively. The age-, sex- and caloric ratio-adjusted HR for all-cause death per 1-SD higher spermidine intake was 0.74 (95% CI: 0.66, 0.83; P < 0.001). Further adjustment for lifestyle factors, established predictors of mortality, and other dietary features yielded an HR of 0.76 (95% CI: 0.67, 0.86; P < 0.001). The association was consistent in subgroups, robust against unmeasured confounding, and independently validated in the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR) Study (age-, sex-, and caloric ratio-adjusted HR per 1-SD higher spermidine intake: 0.71; 95% CI: 0.53, 0.95; P = 0.019). The difference in mortality risk between the top and bottom third of spermidine intakes was similar to that associated with a 5.7-y (95% CI: 3.6, 8.1 y) younger age., Conclusion: Our findings lend epidemiologic support to the concept that nutrition rich in spermidine is linked to increased survival in humans. This trial was registered at www.clinicaltrials.gov as NCT03378843.

A wide range of hybrid biomaterials has been designed in order to sustain bioremediation processes by associating sol-gel SiO₂ matrices with various biologically active compounds (enzymes, antibodies). SiO₂ is a widespread, chemically stable and non-toxic material; thus, the immobilization of enzymes on silica may lead to improving the efficiency of biocatalysts in terms of endurance and economic costs. Our present work explores the potential of different hybrid morphologies, based on hollow tubes and solid spheres of amorphous SiO₂, for enzyme immobilization and the development of competitive biocatalysts. The synthesis protocol and structural characterization of spherical and tubular SiO₂ obtained by the sol gel method were fully investigated in connection with the subsequent immobilization of lipase from Rhizopus orizae . The immobilization is conducted at pH 6, lower than the isoelectric point of lipase and higher than the isoelectric point of silica, which is meant to sustain the physical interactions of the enzyme with the SiO₂ matrix. The morphological, textural and surface properties of spherical and tubular SiO₂ were investigated by SEM, nitrogen sorption, and electrokinetic potential measurements, while the formation and characterization of hybrid organic-inorganic complexes were studied by UV-VIS, FTIR-ATR and fluorescence spectroscopy. The highest degree of enzyme immobilization (as depicted from total organic carbon) was achieved for tubular morphology and the hydrolysis of p-nitrophenyl acetate was used as an enzymatic model reaction conducted in the presence of hybrid lipase⁻SiO₂ complex.

Ketorolac tromethamine is a nonsteroidal anti-inflammatory drug that exhibits analgesic activity with no sedative or anxiolytic properties. Twelve healthy male subjects were enrolled in a study to receive either of 2 treatments over 2 periods in an open-label, randomized, 2-way crossover design: (A) 120 mg of ketorolac tromethamine administered as a continuous subcutaneous infusion over a 24-hour period; or (B) an identical total daily dose administered as 4 intramuscular bolus injections of 30 mg each given every 6 hours (current labeled treatment regimen). The pharmacokinetic and safety profiles were evaluated for both treatments. Both modes of administration have similar values for area under the curve (AUC) and half-life (t 1/2 ), suggesting that continuous subcutaneous infusion and repeated intramuscular bolus injections have similar bioavailability. The peak plasma concentration (C max ) was 40% lower when ketorolac was administered as a continuous subcutaneous infusion compared with repeat intramuscular bolus injections. The concentration at steady-state (C ss ) for continuous subcutaneous infusion was between the C max and C trough values obtained following the 4 intramuscular injections. Both treatment arms were well tolerated., (© 2016, The American College of Clinical Pharmacology.)

A series of SnO 2 -ZnO composite nanostructured (thin) films with different amounts of SnO 2 (from 0 to 50 wt %) was prepared and deposited on a miniaturized porous alumina transducer using the sol-gel and dip coating method. The transducer, developed by our research group, contains Au interdigital electrodes on one side and a Pt heater on the other side. The sensing films were characterized using SEM and AFM techniques. Highly toxic and flammable gases (CO, CO 2 , CH 4 , and C 3 H 8 ) were tested under lab conditions (carrier gas was dry air) using a special gas sensing cell developed by our research group. The gas concentrations varied between 5 and 2000 ppm and the optimum working temperatures were in the range of 210-300 °C. It was found that the sensing performance was influenced by the amount of oxide components present in the composite material. Improved sensing performance was achieved for the ZnO (98 wt %)-SnO 2 (2 wt %) composite as compared to the sensors containing only the pristine oxides. The sensor response, cross-response and recovery characteristics of the analyzed materials are reported. The high sensitivity ( R S = 1.21) to low amounts of CO (5 ppm) was reported for the sensor containing a composite sensitive film with ZnO (98 wt %)-SnO 2 (2 wt %). This sensor response to CO was five times higher as compared to its response to CO 2 , CH 4 , and C 3 H 8 , thus the sensor is considered to be selective for CO under these test conditions.

Raltegravir is a human immunodeficiency virus (HIV)-1 integrase strand transfer inhibitor currently marketed at a dose of 400 mg twice daily (BID). Raltegravir for once daily regimen (QD) at a dose of 1200 mg (2 x 600 mg) is under development and offers a new treatment option for HIV-1 infected treatment-naive subjects. Since raltegravir is eliminated mainly by metabolism via an UDP-glucuronosyltransferase (UGT) 1 A1-mediated glucuronidation pathway, co-administration of UGT1A1 inducers may alter plasma levels of raltegravir. Efavirenz, an UGT1A1 inducer, was used to assess the impact of altered UGT activity on a 1200 mg QD dose of raltegravir. An open label, randomized, 2-period fixed-sequence Phase 1 study was performed in adult healthy male and female subjects (non-childbearing potential) ≥ 19 and ≤55 years of age, with a body mass index (BMI) ≥ 18.5 and ≤32.0 kg/m 2 . Subjects (n = 21) received a single oral dose of 1200 mg raltegravir at bedtime on an empty stomach on Day 1 in Period 1. After a washout period of at least 7 days, subjects received oral doses of 600 mg efavirenz QD at bedtime for 14 consecutive days in Period 2. Subjects received a single oral dose of 1200 mg raltegravir co-administered with 600 mg efavirenz on Day 12 of Period 2. Pharmacokinetic (PK) samples were collected for 72 hours following raltegravir dosing and analyzed using a validated bioanalytical method to quantify raltegravir plasma concentrations. PK parameters were estimated using non-compartmental analysis. Administration of single 1200 mg oral doses of raltegravir alone and co-administered with multiple oral doses of efavirenz were generally well tolerated in healthy subjects. Co-administration with efavirenz yielded geometric mean ratios (GMRs) and their associated 90% confidence intervals (90% CIs) for raltegravir AUC 0-∞, C max , and C 24 of 0.86 (0.73, 1.01), 0.91 (0.70, 1.17), and 0.94 (0.76, 1.17), respectively. The results show that efavirenz modestly reduced the exposure of raltegravir. The reduction in raltegravir exposure is not considered clinically meaningful. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Raltegravir is a human immunodeficiency virus (HIV)-1 integrase strand transfer inhibitor currently marketed at a dose of 400 mg twice-daily (b.i.d.). Raltegravir 1200 mg once-daily (q.d.) (investigational q.d. formulation of 2 × 600 mg tablets; q.d. RAL) was found to be generally well tolerated and non-inferior to the marketed 400 mg b.i.d. dose at 48 weeks in a phase 3 trial. Since raltegravir is eliminated mainly by metabolism via a uridine diphosphate glucuronosyltransferase (UGT) 1A1-mediated glucuronidation pathway, co-administration of UGT1A1 inhibitors may increase the plasma levels of q.d. RAL. To assess this potential, the drug interaction of 1200 mg raltegravir using atazanavir, a known UGT1A1 inhibitor, was studied. An open-label, randomized, 2-period, fixed-sequence phase 1 study was performed in adult healthy male and female (non-childbearing potential) subjects ≥ 19 and ≤ 55 years of age, with a body mass index (BMI) ≥ 18.5 and ≤ 32.0 kg/m 2 . Subjects (n = 14) received a single oral dose of 1200 mg raltegravir in period 1. After a washout period of at least 7 days, the subjects received oral doses of 400 mg atazanavir q.d. for 9 consecutive days, with a single oral dose of 1200 mg raltegravir co-administered on day 7 of period 2. Serial blood samples were collected for 72 h following raltegravir dosing and analysed using a validated bioanalytical method to quantify raltegravir plasma concentrations. Co-administration with atazanavir yielded GMRs (90% CIs) for raltegravir AUC 0-∞ , C max and C 24 of 1.67 (1.34, 2.10), 1.16 (1.01, 1.33) and 1.26 (1.08, 1.46), respectively. There was no effect of raltegravir on serum total bilirubin. In contrast, atazanavir increased the mean bilirubin by up to 200%, an effect that was preserved in the atazanavir/raltegravir treatment group. Administration of single q.d. RAL alone and co-administered with multiple oral doses of atazanavir were generally well tolerated in healthy subjects. The results show that atazanavir increased the PK exposure of raltegravir; therefore, co-administration of atazanavir with raltegravir q.d. is not recommended. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Silicone and Dacron are used in a wide spectrum of implantable and indwelling medical products. They elicit a foreign body response, which results in a chronic inflammatory environment and collagenous encapsulation of the medical device that compromises the immune system's ability to effectively fight infections at the biomaterial surface. The objective of this work is to evaluate a novel process to modify silicone and Dacron with a bioactive collagen surface coupled to a gentamicin impregnated hydrogel graft and assess the surface's cytocompatibility and infection resistance properties. Samples of silicone and polyethylene terephthalate (Dacron velour) were modified by plasma deposition and activation followed by a co-polymer acrylic acid (AA)/acrylamide (AAm) hydrogel graft and covalent immobilization of a bioactive collagen surface. The modified surfaces were characterized using FTIR, contact angle, staining, SEM, and XPS. The poly (AA-AAm) hydrogel was impregnated with gentamicin and tested for controlled release characteristics. Each modified surface was evaluated for its ability to resist infection and to promote normal healing as measured by bacterial growth inhibition (Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa) in both broth and agar conditions as well as using fluorescence microscopy to observe adherence of 3T3-NIH fibroblasts. The addition of the poly (AA-AAm) hydrogel with gentamicin inhibited bacterial growth and the subsequent addition of the collagen surface promoted robust fibroblast adhesion on both silicone and Dacron materials. Thorough surface characterization and in vitro bacterial and fibroblast evaluation results suggest that this novel surface bioengineering process generated a highly effective surface on silicone and Dacron with the potential to reduce infection and promote healing., (© The Author(s) 2015.)

Objective: Pilot study to evaluate computer-guided deep brain stimulation (DBS) programming designed to optimize stimulation settings using objective motion sensor-based motor assessments., Materials and Methods: Seven subjects (five males; 54-71 years) with Parkinson's disease (PD) and recently implanted DBS systems participated in this pilot study. Within two months of lead implantation, the subject returned to the clinic to undergo computer-guided programming and parameter selection. A motion sensor was placed on the index finger of the more affected hand. Software guided a monopolar survey during which monopolar stimulation on each contact was iteratively increased followed by an automated assessment of tremor and bradykinesia. After completing assessments at each setting, a software algorithm determined stimulation settings designed to minimize symptom severities, side effects, and battery usage., Results: Optimal DBS settings were chosen based on average severity of motor symptoms measured by the motion sensor. Settings chosen by the software algorithm identified a therapeutic window and improved tremor and bradykinesia by an average of 35.7% compared with baseline in the "off" state (p < 0.01)., Conclusions: Motion sensor-based computer-guided DBS programming identified stimulation parameters that significantly improved tremor and bradykinesia with minimal clinician involvement. Automated motion sensor-based mapping is worthy of further investigation and may one day serve to extend programming to populations without access to specialized DBS centers., (© 2015 International Neuromodulation Society.)

Objective: We compared the incidence and type of levator ani avulsion diagnosed by translabial ultrasound evaluation in primiparous women six months after vacuum-assisted or spontaneous vaginal delivery., Material and Methods: This retrospective observational study was performed between January 2011 and December 2013. Primiparous women six months after vacuum-assisted vaginal delivery and after spontaneous vaginal delivery underwent translabial ultrasound evaluation. The distance between the urethra and fibers of the musculus levator ani puborectalis (levator-urethra gap) was measured. A levator-urethra gap >25 mm was considered a musculus levator ani avulsion., Results: In total, 184 women participated in the study. Among them, 92 had vacuum extraction and 92 had uncomplicated spontaneous delivery. A longer levator-urethra gap on both sides of the pubic bone was found in women after vacuum-assisted vaginal delivery (p < 0.0001 for both sides). Musculus levator ani avulsion was identified in 20 women (unilateral in 16 cases and bilateral in four cases). No difference in an incidence of musculus levator ani avulsion was identified in women after vacuum-assisted vaginal delivery [11/92 (12%)] compared to spontaneous delivery [9/92 (10%); p = 0.81]., Conclusion: Vacuum-assisted vaginal delivery in primiparous women is associated with a longer levator-urethra gap but not with a higher frequency of avulsion of the musculus levator ani.

Introduction: The current practice of percutaneous subxiphoid needle access to the "healthy" pericardial sac has significant limitations. We sought to examine the feasibility of a novel toolkit designed to improve this procedure., Methods and Results: The toolkit included a pericardial access needle and a virtual imaging platform. The needle had a 0.036 inch outer diameter, abbreviated 25° bevel, and was electrically insulated except for two small surfaces recessed from the tip. Radiofrequency energy was delivered via these surfaces to facilitate pericardial perforation. The virtual imaging system demonstrated the needle in real time and in its entirety within the thoracic anatomy of the individual animal, which was reconstructed from computed tomographic images obtained preoperatively and registered to the operative field. In five large (40-60 kg) healthy pigs, percutaneous subxiphoid access to the sac using both anterior and posterior approaches was performed. Spatial inaccuracy was measured as the distance between the pericardial puncture site and the anterior or posterior descending coronary artery, the pericardium contiguous to which had been targeted by the needle. In each animal, pericardial access was gained at 4 discrete sites (2 anterior, 2 posterior). Inaccuracy was 4.2 ± 2.2 millimeters (range 0-8 millimeters) and did not differ significantly between anterior and posterior approaches. No damage to the epicardium or coronary arteries was observed., Conclusions: Percutaneous subxiphoid access to the pericardial sac utilizing this toolkit was feasible, including safety and reasonable accuracy., (© 2015 Wiley Periodicals, Inc.)

Ethnic socialization and ethnic identity have been related to positive outcomes, but little research has examined these associations longitudinally. This three-wave study prospectively linked socialization messages at Time 1, ethnic identity and American identity at Time 2, and self-esteem and depressive symptoms at Time 3 in 147 (58% female; 25% first-generation) Asian-American adolescents. The results indicated positive links between cultural socialization messages and ethnic and American identity, though the latter association was significant only for females. Ethnic identity was positively related to self-esteem, and mediated the positive effect of cultural socialization on self-esteem. The promotion of mistrust was positively linked to self-esteem and negatively related to ethnic identity, though this latter association was significant for foreign-born youth only. Our findings highlight the importance of elucidating prospective links in identity development, and examining gender and generational differences within them.

Nonpersistent pesticides are considered less harmful for the environment, but their impact as endocrine disruptors has not been fully explored. The pesticide Switch was applied to grape vines, and the maximum residue concentration of its active ingredients was quantified. The transactivation potential of the pesticides Acorit, Frupica, Steward, Reldan, Switch, Cantus, Teldor, and Scala and their active compounds (hexythiazox, mepanipyrim, indoxacarb, chlorpyrifos-methyl, cyprodinil, fludioxonil, boscalid, fenhexamid, and pyrimethanil) were tested on human estrogen receptor α (ERα), androgen receptor (AR) and arylhydrocarbon receptor (AhR) in vitro. Relative binding affinities of the pure pesticide constituents for AR and their effect on human breast cancer and prostate cancer cell lines were evaluated. Residue concentrations of Switch's ingredients were below maximum residue limits. Fludioxonil and fenhexamid were ERα agonists (EC50 -values of 3.7 and 9.0 μM, respectively) and had time-dependent effects on endogenous ERα-target gene expression (cyclin D1, progesterone receptor, and nuclear respiratory factor 1) in MCF-7 human breast cancer cells. Fludioxonil, mepanipyrim, cyprodinil, pyrimethanil, and chlorpyrifos-methyl were AhR-agonists (EC50 s of 0.42, 0.77, 1.4, 4.6, and 5.1 μM, respectively). Weak AR binding was shown for chlorpyrifos-methyl, cyprodinil, fenhexamid, and fludioxonil. Assuming a total uptake which does not take metabolism and clearance rates into account, our in vitro evidence suggests that pesticides could activate pathways affecting hormonal balance, even within permitted limits, thus potentially acting as endocrine disruptors., (Copyright © 2013 Wiley Periodicals, Inc., a Wiley company.)