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BackgroundSlow-paced breathing training (6 breaths per minute [BPM]) improves physiological and psychological well-being by inducing relaxation characterized by increased heart rate variability (HRV). However, classic breathing training has a limited target group, and retention rates are very low. Although a gameful approach may help overcome these challenges, it is crucial to enable breathing training in a scalable context (eg, smartphone only) and ensure that they remain effective. However, despite the health benefits, no validated mobile gameful breathing training featuring a biofeedback component based on breathing seems to exist. ObjectiveThis study aims to describe the design choices and their implementation in a concrete mobile gameful breathing training app. Furthermore, it aims to deliver an initial validation of the efficacy of the resulting app. MethodsPrevious work was used to derive informed design choices, which, in turn, were applied to build the gameful breathing training app Breeze. In a pretest (n=3), design weaknesses in Breeze were identified, and Breeze was adjusted accordingly. The app was then evaluated in a pilot study (n=16). To ascertain that the effectiveness was maintained, recordings of breathing rates and HRV-derived measures (eg, root mean square of the successive differences [RMSSDs]) were collected. We compared 3 stages: baseline, standard breathing training deployed on a smartphone, and Breeze. ResultsOverall, 5 design choices were made: use of cool colors, natural settings, tightly incorporated game elements, game mechanics reflecting physiological measures, and a light narrative and progression model. Breeze was effective, as it resulted in a slow-paced breathing rate of 6 BPM, which, in turn, resulted in significantly increased HRV measures compared with baseline (P

Fire is a global disturbance that is predicted to increase in frequency and severity in many parts of the world due to climate change. Biological soil crust (biocrust) communities are often overlooked in fire studies despite having a substantial effect on ecological function and the adjacent communities. The goal of this study is to synthesize and analyze existing data elucidating the recovery of biocrust cover following fire at the global-scale and suggest avenues for future research. We performed a meta-analysis of studies from 1984 to 2019 to address the response of biocrust after fire and determine the moderating factors governing their response. Overall, fire reduced biocrust cover by 50% and had a significantly negative effect on biocrusts classified as cyanobacteria or algal dominated. Additionally, as time since fire increased, total biocrust cover increased but this response was modulated by biocrust type indicating compliance with traditional biocrust successional models. However, there was significant unexplained heterogeneity within the meta-analysis. This reflects a critical need for more studies specifically addressing the effect of fire on biocrust communities as they are an ecosystem engineer in drylands around the world. We suggest more thorough characterization of biocrust organisms through field and laboratory studies to understand the mechanisms of biocrust response to fire. Additionally, research is needed across a broader geographic range to represent the known distribution of biocrust communities, particularly as fires increase in severity and scope.

Oil palm interspecific hybrids Elaeis oleífera × Elaeis guineensis (O × G) are grown across approximately 68,000 hectares in Colombia. To address the limited natural pollination capacity of O × G hybrids and the difficulties associated with assisted pollination regarding the timing of E. guineensis pollen application, the Colombian Oil Palm Research Center (Cenipalma) conducted studies on induction of parthenocarpic fruits. Cenipalma confirmed that application of 1,200 ppm of 1-naphthaleneacetic acid (NAA) at different phenological stages enabled the formation of parthenocarpic fruits. This technological advance was termed artificial pollination. This paper presents the results from a research study aimed at assessing the labor productivity for two methods of NAA application (NAA in solid mixture and NAA in liquid suspension). From a methodological standpoint, a time and motion study was conducted to assess labor productivity for each NAA application method, with time data collected using the software Cybertracker on a mobile platform (smartphone). The results indicated that a worker can cover 3.9 hectares in a working day and sprinkle 303 inflorescences in a working day when applying NAA in solid mixture. On the other hand, when applying NAA in liquid suspension, the worker can cover 3.2 hectares and sprinkle 315 inflorescences (i.e. in a working day).

Introducción y justificación: La afección bucofaríngea, y más concretamente el dolor de garganta, por su prevalencia y relación con el uso inadecuado de medicamentos tiene una alta importancia en salud, el farmacéutico contribuye a que el usuario alcance una automedicación adecuada a través de los servicios de atención farmacéutica. Sin embargo, se conoce poco en el ámbito de la farmacia comunitaria sobre los usuarios que demandan esta atención, así como las consultas e intervenciones de los farmacéuticos. Aplicabilidad de los resultados: Conocer las características de la demanda y la práctica farmacéutica en afección bucofaríngea permitirá establecer estrategias sanitarias destinadas a optimizar la asistencia sanitaria. Objetivos: Caracterizar la práctica farmacéutica en afección bucofaríngea realizada en farmacias comunitarias españolas. Material y métodos: Estudio observacional descriptivo transversal. En farmacias comunitarias voluntarias del territorio español. La población de estudio serán los usuarios que acudan a las farmacias por una afección bucofaríngea. La duración del trabajo de campo será de tres meses. Las variables contempladas en el estudio serán aquellas que caracterizan al usuario, a la consulta realizada, y a la intervención del farmacéutico. Se realizará un análisis estadístico descriptivo de los datos (univariante y multivariante por la técnica de correspondencias múltiples). Se garantizará la confidencialidad y el consentimiento informado de los participantes.

Título en ingles: Embryos rescue for the obtaining of grapevine (Vitis vinifera L.) vitroplants Resumen: Este trabajo es la primera fase de un macroproyecto sobre la optimización de un protocolo para la obtención de metabolitos secundarios de interés comercial mediante la utilización de suspensiones celulares de Vid (Vitis vinífera L.). Se investigó el rescate de embriones como alternativa para la obtención de vitroplantas de vid (Vitis vinífera L.). El material vegetal utilizado se obtuvo de frutos de vid variedad Red Globe comerciales. Las semillas se desinfectaron sumergiéndolas en 5 g/l de ácido dicloroisocianúrico (NaDCC) por 15 min y luego en 2 g/l de Benomyl® por 15 min, con una efectividad del 92%. Se realizaron diferentes tratamientos para la obtención de plántulas utilizando semillas como explantes, las cuales se cultivaron en el medio Murashige Skoog suplementado con diferentes concentraciones de ácido indolacético (AIA) en combinación con ácido giberélico (AG3) y kinetina (K) sin obtener respuesta favorable para la germinación. Como alternativa, se extrajeron semillas inmaduras de frutos de la planta y se colocaron en el mismo medio pero suplementado con 100 mg/l de polivinilpirrolidona (PVP), 0.35 mg/l de AG3 y 1.75 mg/l de AIA por un mes. Posteriormente, se abrieron las semillas y se realizó el rescate de embriones, sembrándolos bajo condiciones de oscuridad por ocho días en los medios de cultivo Murashige Skoog 1 y 2 modificados, encontrando la formación de vitroplantas en un 40% al mes de cultivo. Palabras clave: cultivo in vitro, reguladores de crecimiento, ácido dicloroisocianúrico, Red Globe. Abstract: This work is the first phase of a macroproyect about the optimization of a protocol for the obtaining of secondary metabolites of commercial interest by means of the use of cellular suspensions of Vitis vinífera L. The embryos rescue was investigated as alternative for the obtaining of grapevine (Vitis vinífera L.) vitroplants. The vegetable material used was obtained from commercial fruits of grapevine Red Globe variety. The seeds were disinfected submerging them in 5 g/l of dicloroisocianuric acid (NaDCC) for 15 min, and then in Benomyl® 2 g/l for 15 min, with an effectiveness of 92%. Different treatments were performed to obtain plants using seeds as explants, which were cultured on Murashige Skoog medium supplemented with different concentrations of indole acetic acid (AIA) in combination with gibberellic acid (AG3) and kinetin (K) without obtaining favorable answer for the germination. As alternative, immature seeds were extracted from grape fruits and placed on Murashige Skoog medium supplemented with 100 mg/l polyvinyl pyrrolidone (PVP), 0.35 mg/l of gibberellic acid and 1.75 mg/l of indol acetic acid for a month. Seeds were then opened and performed embryo rescue, planting them under dark conditions for eight days in the culture media Murashige Skoog 1 and 2 modified, finding plants formation by 40% a month after growing. Key words: in vitro culture, growth regulators, dichloroisocyanuric acid, Red Globe.

In this study the ozonized olive and sunflower oils are chemical and microbiologically compared. These oils were introduced into a reactor with bubbling ozone gas in a water bath at room temperature until they were solidified. The peroxide, acidity and iodine values along with antimicrobial activity were determined. Ozonization effects on the fatty acid composition of these oils were analyzed using Gas-Liquid Chromatographic Technique. An increase in peroxidation and acidity values was observed in both oils but they were higher in ozonized sunflower oil. Iodine value was zero in ozonized olive oil whereas in ozonized sunflower was 8.8 g Iodine per 100 g. The antimicrobial activity was similar for both ozonized oils except for Minimum Bactericidal Concentrations of Pseudomona aeruginosa. Composition of fatty acids in both ozonized oils showed gradual decrease in unsaturated fatty acids (C18:1, C18:2) with gradual increase in ozone doses.

Este artículo estudia un conjunto de seis loas representadas en carros triunfales como parte de la fiesta llevada a cabo en Querétaro en 1738, con motivo de la inauguración de su acueducto. Aunque la historiografía y la crítica de la literatura novohispana no suelen considerar este tipo de textos, se pretende demostrar que las loas escritas para carro triunfal constituyen una de las modalidades del género dramático breve loa, cercano por sus características formales y escénicas a la loa cortesana, pero con una marcada función ecfrástico-explicativa del aparato efímero que le sirve al mismo tiempo de referente alegórico y de marco físico de representación. Por otra parte, por la notable presencia de la música, el canto y el estilo recitativo, representan una muestra del proceso de musicalización al modo italiano de este género en la praxis novohispana.

This work was carried out at the greenhouse with de purpose of analyzing the influence of some chemical rectifications on the chemical and agronomic behavior of twelve samples of soils from the Colombian Tropical dry forest; some of these showed high levels of salinity of sodium and magnesium; another organic soil was highley acid-aluminium and magnesium, and other with a very low fertility. The trials were based upon an experimental desing completely at random. Each soil was given three chemical rectifications at two levels or doses, and leaching; a control was just given the leaching. All of the treatments were given two leachings during the essay and two productions of dry matter of sorghum - as the reference plant- were evaluated. At the first essay was proposed to lower until 10 and 5 % of sodium saturation or 20 and 10% of magnesium saturation; in a second essay were applied 50 and 25 t/ha of each chemical rectification; for the third essay the applied doses were 20, 10 and 5 t/ha organic rectifications, such manure and poultry bedding, With the leaching was lowered the salinity in all the soils, below 3 dSm -1; the chemical rectifications, below 4 dS-1; in the majority of the soils. The magnesium and sodium saturation were satisfied in the majority of the treatments using gypsum and sulfuric acid. The pHs were reduced in 95 % in all the soils, but this occurred with most intensity with the sulfuric acid and sulfur than using gypsum. The best physical properties of the soils do not implied that they respond as well in their dry matter productions. Acidic or magnesic soils are best rectified with gypsum. The highest doses of organic rectifications favored the dry matter production.El trabajo se realizó en el invernadero de la Facultad de Ciencias Agropecuarias de Palmira, con 12 suelos del Bosque Seco Tropical Colombiano que presentaban problemas de salinidad, sodio y magnesio; un suelo orgánico fuertemente ácido alumínico-magnésico y otro con muy baja fertilidad. Los ensayos se diseñaron completamente al azar. Cada suelo recibió tres enmiendas químicas en dos niveles o dosis y lavado; el testigo sólo recibió lavado. Todos los tratamientos recibieron dos lavados durante el ensayo y se evaluaron dos producciones de materia seca de sorgo como planta indicadora. En un primer ensayo se propuso rebajar a 10 y 5% de saturación de sodio ó 20 y 10% de saturación de magnesio; en un segundo ensayo se aplicaron 50 y 25 t/ha de cada enmienda química; para el tercer ensayo, las dosis aplicadas fueron de 20, 10 y 5 t/ha de enmiendas orgánicas como gallinaza y estiércol en este caso. Con el solo lavado se logró reducir la salinidad de todos los suelos por debajo de 3 dSm-1; con las enmiendas orgánicas por debajo de 4 dSnf1 en la mayoría de los suelos. La saturación de sodio y de magnesio fueron satisfechos en la mayoría de los tratamientos con yeso y ácido sulfúrico. Los pHs se redujeron en 95 % de todos los suelos pero ocurrió con mayor intensidad con las enmiendas ácido sulfúrico y azufre que con yeso. Las mejores propiedades físicas no implican que los suelos respondan también en sus producciones de materia seca. En suelos ácidos o magnésicos es preferible su recuperación con yeso. La dosis altas de enmiendas orgánicas favorecieron la producción de materia seca.

Abstract Background The incidence of primary osteoporosis is higher in Japan than in USA and European countries. Recently, the importance of preventive medicine has been gradually recognized in the field of orthopaedic surgery with a concept that peak bone mass should be increased in childhood as much as possible for the prevention of osteoporosis. Under such background, we have developed a new bean snack with an aim to improve bone volume loss. In this study, we examined the effects of a newly developed snack on bone volume and density in osteoporosis model mice. Methods Orchiectomy (ORX) and ovariectomy (OVX) were performed for C57BL/6J mice of twelve-week-old (Jackson Laboratory, Bar Harbar, ME, USA) were used in this experiment. We prepared and given three types of powder diet e.g.: normal calcium diet (NCD, Ca: 0.9%, Clea Japan Co., Tokyo, Japan), low calcium diet (LCD, Ca: 0.63%, Clea Japan Co.,) and special diet (SCD, Ca: 0.9%). Eighteen weeks after surgery, all the animals were sacrified and prepared for histomorphometric analysis to quantify bone density and bone mineral content. Results As a result of histomorphometric examination, SCD was revealed to enhance bone volume irrespective of age and sex. The bone density was increased significantly in osteoporosis model mice fed the newly developmental snack as compared with the control mice. The bone mineral content was also enhanced significantly. These phenomena were revealed in both sexes. Conclusion It is shown that the newly developed bean snack is highly effective for the improvement of bone volume loss irrespective of sex. We demonstrated that newly developmental snack supplements may be a useful preventive measure for Japanese whose bone mineral density values are less than the ideal condition.

Opportunistic bacterial pathogens must compete with other bacteria and switch between host- and environment-adapted states. Type VI secretion systems (T6SSs) occur widely in gram-negative bacteria and can efficiently kill neighboring competitors. We determined the distribution of T6SSs across the genus Serratia and observed that a highly conserved antibacterial T6SS is differentially active between closely related clinical isolates of Serratia marcescens. By combining genomic and experimental approaches, we identified a genus-core two-component system, BetR-Reg1-Reg2, that controls T6SS activity and exhibits frequent inactivating mutations, exclusively in S. marcescens isolates of clinical origin. This regulatory system controls a number of lifestyle-related traits at transcriptional and post-translational levels, including T6SS activity, antibiotic production, motility, and adhesion, with loss of BetR increasing virulence in an in vivo infection model. Our data support a model whereby this system represents a conserved, modular switch from sessile to pioneering and aggressive behavior, which is subject to selection pressure in clinical environments., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Drug-induced hearing injury (ototoxicity) is a common, debilitating side effect of many antibiotic regimens that can be worsened by adverse drug interactions. Such adverse drug interactions are often not detected until after drugs are already on the market because of the difficulty of measuring all possible drug combinations. While in vivo mammalian assays to screen for ototoxic damage exist, they are currently time-consuming, costly, and limited in throughput, which limits their utility in assessing drug interaction outcomes. To facilitate more rapid quantification of ototoxicity and assessment of adverse drug interactions that impact ototoxicity, we have developed a high-throughput workflow we call parallelized evaluation of protection and injury for toxicity assessment (PEPITA). PEPITA uses zebrafish larvae to quantify ototoxic damage and protection. Previous work has shown that hair cells (HCs) in the zebrafish lateral line are very similar to human inner ear HCs, meaning zebrafish are a viable model to test drug-induced ototoxicity. In PEPITA, we expose zebrafish larvae to different combinations of drugs, fluorescently label the HCs, and subsequently use microscopy to quantify the brightness of the fluorescently labeled HCs as an assay for ototoxic damage and hair-cell viability. PEPITA is a reproducible, low-cost, technically accessible, and high-throughput assay. These advantages allow many experiments to be conducted in parallel, paving the way for systematic evaluation of drug-induced hearing injury and other multidrug interactions. Key features • Analysis of drug-induced hair cell damage associated with ototoxicity using Danio rerio • Ototoxicity assessment performed in vivo • Uses microscopy to generate images to assay ototoxicity quantitatively. • Enables testing of various combinations of drugs at various doses to determine toxicity-associated drug-drug interaction outcomes (synergy, antagonism)., Competing Interests: Competing interestsThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (©Copyright : © 2024 The Authors; This is an open access article under the CC BY-NC license.)

Introduction: Ototoxicity is a debilitating side effect of over 150 medications with diverse mechanisms of action, many of which could be taken concurrently to treat multiple conditions. Approaches for preclinical evaluation of drug-drug interactions that might impact ototoxicity would facilitate design of safer multi-drug regimens and mitigate unsafe polypharmacy by flagging combinations that potentially cause adverse interactions for monitoring. They may also identify protective agents that antagonize ototoxic injury. Methods: To address this need, we have developed a novel workflow that we call Parallelized Evaluation of Protection and Injury for Toxicity Assessment (PEPITA), which empowers high-throughput, semi-automated quantification of ototoxicity and otoprotection in zebrafish larvae via microscopy. We used PEPITA and confocal microscopy to characterize in vivo the consequences of drug-drug interactions on ototoxic drug uptake and cellular damage of zebrafish lateral line hair cells. Results and discussion: By applying PEPITA to measure ototoxic drug interaction outcomes, we discovered antagonistic interactions between macrolide and aminoglycoside antibiotics that confer protection against aminoglycoside-induced damage to lateral line hair cells in zebrafish larvae. Co-administration of either azithromycin or erythromycin in zebrafish protected against damage from a broad panel of aminoglycosides, at least in part via inhibiting drug uptake into hair cells via a mechanism independent from hair cell mechanotransduction. Conversely, combining macrolides with aminoglycosides in bacterial inhibition assays does not show antagonism of antimicrobial efficacy. The proof-of-concept otoprotective antagonism suggests that combinatorial interventions can potentially be developed to protect against other forms of toxicity without hindering on-target drug efficacy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Bustad, Mudrock, Nilles, Mcquate, Bergado, Gu, Galitan, Gleason, Ou, Raible, Hernandez and Ma.)

Postsynthetic modification (PSM) of metal-organic frameworks (MOFs) provides access to functional materials and advanced porous solid engineering. Herein, we report the reversible PSM of a multivariate isoreticular MOF by applying dynamic furan-maleimide Diels-Alder (DA) chemistry. The key step involves incorporating a furan group into the MOF via "click" PSM, which can then undergo repeated cycles of modification and de-modification with maleimides. The structural integrity, crystallinity, and porosity of the furan-appended MOF remained intact even after three consecutive PSM/de-modification cycles using three different functionalized maleimides., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Antibacterial activity assays are an important tool in the assessment of the ability of one bacterium to kill or inhibit the growth of another, for example, during the study of the Type VI secretion system (T6SS) and the antibacterial toxins it secretes. The method we describe here can detect the ability of a bacterial strain to kill or inhibit other bacterial cells in a contact-dependent manner when cocultured on an agar surface. It is particularly useful since it enumerates the recovery of viable target cells and thus enables quantification of the antibacterial activity. We provide a detailed description of how to measure the T6SS-dependent antibacterial activity of a bacterium such as Serratia marcescens against a competitor prokaryotic organism, Escherichia coli, and describe possible variations in the method to allow adaptation to other attacker and target organisms., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Ototoxicity is a debilitating side effect of over 150 medications with diverse mechanisms of action, many of which could be taken concurrently to treat multiple conditions. Approaches for preclinical evaluation of drug interactions that might impact ototoxicity would facilitate design of safer multi-drug regimens and mitigate unsafe polypharmacy by flagging combinations that potentially cause adverse interactions for monitoring. They may also identify protective agents that antagonize ototoxic injury. To address this need, we have developed a novel workflow that we call Parallelized Evaluation of Protection and Injury for Toxicity Assessment (PEPITA), which empowers high-throughput, semi-automated quantification of ototoxicity and otoprotection in zebrafish larvae. By applying PEPITA to characterize ototoxic drug interaction outcomes, we have discovered antagonistic interactions between macrolide and aminoglycoside antibiotics that confer protection against aminoglycoside-induced damage to lateral line hair cells in zebrafish larvae. Co-administration of either azithromycin or erythromycin in zebrafish protected against damage from a broad panel of aminoglycosides, at least in part via inhibiting drug uptake into hair cells via a mechanism independent from hair cell mechanotransduction. Conversely, combining macrolides with aminoglycosides in bacterial inhibition assays does not show antagonism of antimicrobial efficacy. The proof-of-concept otoprotective antagonism suggests that combinatorial interventions can potentially be developed to protect against other forms of toxicity without hindering on-target drug efficacy.

Background: People with cystic fibrosis (PwCF) have chronic lung disease and may be at increased risk of coronavirus disease 2019 (COVID-19)-related morbidity and mortality. This study aimed to determine seroprevalence and clinical characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children with cystic fibrosis (CF), and to assess antibody responses following SARS-CoV-2 infection or vaccination., Methods: Children and adolescents with CF followed at Seattle Children's Hospital were enrolled between July 20, 2020 and February 28, 2021. SARS-CoV-2 serostatus was determined on enrollment at 6 and 11 months (±2 months) for nucleocapsid and spike IgG. Participants completed intake and weekly surveys inquiring about SARS-CoV-2 exposures, viral/respiratory illnesses, and symptoms., Results: Of 125 PwCF enrolled, 14 (11%) had positive SARS-CoV-2 antibodies consistent with recent or past infection. Seropositive participants were more likely to identify as Hispanic (29% vs. 8%, p = 0.04) and have pulmonary exacerbations requiring oral antibiotics in the year prior (71% vs. 41%, p = 0.04). Five seropositive individuals (35.7%) were asymptomatic, while six (42.9%) reported mild symptoms, primarily cough and nasal congestion. Antispike protein IgG levels were approximately 10-fold higher in participants following vaccination compared with participants who had natural infection alone (p < 0.0001) and resembled levels previously reported in the general population., Conclusions: A majority of PwCF have mild or no symptoms of SARS-CoV-2 making it difficult to distinguish from baseline respiratory symptoms. Hispanic PwCF may be disproportionately impacted, consistent with racial and ethnic COVID-19 disparities among the general US population. Vaccination in PwCF generated antibody responses similar to those previously reported in the general population., (© 2023 Wiley Periodicals LLC.)

Near-infrared (NIR) emitting phosphors are currently receiving considerable attention owing to their high demand in various applications, such as light detection and ranging (LiDAR), short-range communications, security, biosensing and night vision lighting applications. The miniaturization of photonic components demands the integration of thin films into exploitable devices. In this context, NIR emitting ZnAl 2 O 4 :Ce/Nd films of hundreds of nanometer thickness are synthesized using a scalable and cost-efficient approach to screen printing. Cerium co-doping is responsible for the Nd emission in the NIR through energy transfer by exciting the films under UV excitation at around 360 nm. Through the proper design of ink, dense Nd/Ce doped ZnAl 2 O 4 ceramic films were produced using polycrystalline alumina. The use of polycrystalline alumina substrates opens up new opportunities because this ceramic is a cheap and well-known substrate for optoelectronic packaging. During manufacturing, as a direct effect of predominant crystal growth over the polycrystalline alumina substrate, an increase in emission intensity is achieved. The results obtained by X-ray photoelectron (XPS) and X-ray absorption near edge spectroscopy (XANES) serve to determine the oxidation state of Ce. The findings of this study indicate that a higher concentration of Ce 4+ promotes NIR emission. This study may contribute to a better understanding of film production processes of films based on the ZnAl 2 O 4 matrix and guide future studies on films for NIR emitters.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy that harbors mutations in homologous recombination-repair (HR-repair) proteins in 20%-25% of cases. Defects in HR impart a specific vulnerability to poly ADP ribose polymerase inhibitors and platinum-containing chemotherapy in tumor cells. However, not all patients who receive these therapies respond, and many who initially respond ultimately develop resistance. Inactivation of the HR pathway is associated with the overexpression of polymerase theta (Polθ, or POLQ). This key enzyme regulates the microhomology-mediated end-joining (MMEJ) pathway of double-strand break (DSB) repair. Using human and murine HR-deficient PDAC models, we found that POLQ knockdown is synthetically lethal in combination with mutations in HR genes such as BRCA1 and BRCA2 and the DNA damage repair gene ATM. Further, POLQ knockdown enhances cytosolic micronuclei formation and activates signaling of cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING), leading to enhanced infiltration of activated CD8+ T cells in BRCA2-deficient PDAC tumors in vivo. Overall, POLQ, a key mediator in the MMEJ pathway, is critical for DSB repair in BRCA2-deficient PDAC. Its inhibition represents a synthetic lethal approach to blocking tumor growth while concurrently activating the cGAS-STING signaling pathway to enhance tumor immune infiltration, highlighting what we believe to be a new role for POLQ in the tumor immune environment.

Deep-UV (180-280 nm) phosphors have attracted tremendous interest in tri-band-based white light-emitting diode (LED) technology, bio- and photochemistry, as well as various medical fields. However, the application of many UV-emitting materials has been hindered due to their poor thermal or chemical stability, complex synthesis, and environmental harmfulness. A particular concern is posed by the utilization of rare earths affected by rising price and depletion of natural resources. As a consequence, the development of phosphors without rare-earth elements represents an important challenge. In this work, as a potential UV-C phosphor, undoped ZnAl 2 O 4 fibers have been synthesized by a cost-efficient wet chemical route. The rare-earth-free ZnAl 2 O 4 nanofibers exhibit a strong UV emission with two bands peaking at 5.4 eV (230 nm) and 4.75 eV (261 nm). The emission intensity can be controlled by tuning the Zn/Al ratio. A structure-property relationship has been thoroughly studied to understand the origin of the UV emission. For this reason, ZnAl 2 O 4 nanofibers have been analyzed by X-ray absorption near-edge structure (XANES), extended X-ray absorption fine structure (EXAFS), X-ray diffraction (XRD), and Raman spectroscopy techniques showing that a normal spinel structure of the synthesized material is preserved within a wide range of Zn/Al ratios. The experimental evidence of a strong and narrow band at 7.04 eV in the excitation spectrum of the 5.4 eV emission suggests its excitonic nature. Moreover, the 4.75 eV emission is shown to be related to excitons perturbed by lattice defects, presumably oxygen or cation vacancies. These findings shed light on the design of UV-C emission devices for sterilization based on a rare-earth-free phosphor, providing a feasible alternative to the conventional phosphors doped with rare-earth elements.

Breast cancer (BCa) is the most common type of cancer affecting women worldwide. Some histological subtypes of benign breast disease (BBD) are considered risk factors for developing BCa. Single nucleotide polymorphisms (SNPs) in the genes encoding apolipoproteins A-I ( APOA1 ) and B ( APOB ) have been associated with BCa in Tunisian, Chinese, and Taiwanese populations. The objective of this pilot study is to evaluate the possible contribution of APOA1 and APOB polymorphisms to BCa and BBD in the Mexican population. We analyzed the association of 4 SNPs in genes encoding apolipoproteins: rs670 and rs5069 in the APOA1 gene, and rs693 and rs1042031 in the APOB gene, by performing PCR-RFLP with DNA extracted from the biopsy tissue of Mexican women with BCa or BBD and whole blood samples obtained from the general population (GP). Our results showed an association between the CT + TT genotypes of the SNP rs5069 and BBD ( p = 0.03201). In the A-T haplotype, the frequency of the SNPs rs670 and rs5069 differed significantly between the BBD group and the GP and BCa groups ( p = 0.004111; p = 0.01303). In conclusion, the SNP rs5069 is associated with BBD but not with BCa in the Mexican population.

Background: The neuroimmune system is required for normal neural processes, including modulation of cognition, emotion, and adaptive behaviors. Aberrant neuroimmune activation is associated with dysregulation of memory and emotion, though the precise mechanisms at play are complex and highly context dependent. Sex differences in neuroimmune activation and function further complicate our understanding of its roles in cognitive and affective regulation., Methods: Here, we characterized the physiological sickness and inflammatory response of the hippocampus following intracerebroventricular (ICV) administration of a synthetic viral mimic, polyinosinic:polycytidylic acid (poly I:C), in both male and female C57Bl/6N mice., Results: We observed that poly I:C induced weight loss, fever, and elevations of cytokine and chemokines in the hippocampus of both sexes. Specifically, we found transient increases in gene expression and protein levels of IL-1α, IL-1β, IL-4, IL-6, TNFα, CCL2, and CXCL10, where males showed a greater magnitude of response compared with females. Only males showed increased IFNα and IFNγ in response to poly I:C, whereas both males and females exhibited elevations of IFNβ, demonstrating a specific sex difference in the anti-viral response in the hippocampus., Conclusion: Our data suggest that type I interferons are one potential node mediating sex-specific cytokine responses and neuroimmune effects on cognition. Together, these findings highlight the importance of using both males and females and analyzing a broad set of inflammatory markers in order to identify the precise, sex-specific roles for neuroimmune dysregulation in neurological diseases and disorders., (© 2021. The Author(s).)

Interest in luminescent materials has been continuously growing for several decades, looking for the development of new systems with optimized optical properties. Nowadays, research has been focused on the development of materials that satisfy specific market requirements in optoelectronics, radioelectronics, aerospace, bio-sensing, pigment applications, etc. Despite the fact that several efforts have made in the synthesis of organic luminescent materials, their poor stability under light exposure limits their use. Hence, luminescent materials based on inorganic phosphors are considered a mature topic. Within this subject, glass, glass-ceramics and ceramics have had great technological relevance, depending on the final applications. Supposing that luminescent materials are able to withstand high temperatures, have a high strength and, simultaneously, possess high stability, ceramics may be considered promising candidates to demonstrate required performance. In an ongoing effort to find a suitable synthesis method for their processing, some routes to develop nanostructured luminescent materials are addressed in this review paper. Several ceramic families that show luminescence have been intensively studied in the last few decades. Here, we demonstrate the synthesis of particles based on aluminate using the methods of sol-gel or molten salts and the production of thin films using screen printing assisted by a molten salt flux. The goal of this review is to identify potential methods to tailor the micro-nanostructure and to tune both the emission and excitation properties, focusing on emerging strategies that can be easily transferred to an industrial scale. Major challenges, opportunities, and directions of future research are specified.

The use of photonic concepts to achieve nanoactuation based on light triggering requires complex architectures to obtain the desired effect. In this context, the recent discovery of reversible optical control of the domain configuration in ferroelectrics offers a light-ferroic interplay that can be easily controlled. To date, however, the optical control of ferroelectric domains has been explored in single crystals, although polycrystals are technologically more desirable because they can be manufactured in a scalable and reproducible fashion. Here we report experimental evidence for a large photostrain response in polycrystalline BaTiO 3 that is comparable to their electrostrain values. Domains engineering is performed through grain size control, thereby evidencing that charged domain walls appear to be the functional interfaces for the light-driven domain switching. The findings shed light on the design of high-performance photoactuators based on ferroelectric ceramics, providing a feasible alternative to conventional voltage-driven nanoactuators.

Pseudomonas aeruginosa is a common respiratory pathogen in cystic fibrosis (CF) patients which undergoes adaptations during chronic infection towards reduced virulence, which can facilitate bacterial evasion of killing by host cells. However, inflammatory cytokines are often found to be elevated in CF patients, and it is unknown how chronic P. aeruginosa infection can be paradoxically associated with both diminished virulence in vitro and increased inflammation and disease progression. Thus, we investigated the relationship between the stimulation of inflammatory cell death pathways by CF P. aeruginosa respiratory isolates and the expression of key inflammatory cytokines. We show that early respiratory isolates of P. aeruginosa from CF patients potently induce inflammasome signaling, cell death, and expression of IL-1β by macrophages, yet little expression of other inflammatory cytokines (TNF, IL-6 and IL-8). In contrast, chronic P. aeruginosa isolates induce relatively poor macrophage inflammasome signaling, cell death, and IL-1β expression but paradoxically excessive production of TNF, IL-6 and IL-8 compared to early P. aeruginosa isolates. Using various mutants of P. aeruginosa, we show that the premature cell death of macrophages caused by virulent bacteria compromises their ability to express cytokines. Contrary to the belief that chronic P. aeruginosa isolates are less pathogenic, we reveal that infections with chronic P. aeruginosa isolates result in increased cytokine induction due to their failure to induce immune cell death, which results in a relatively intense inflammation compared with early isolates.

Coronavirus disease 2019 (COVID-19) can present with abdominal pain in children and adults. Most imaging findings have been limited to characteristic lung findings, as well as one report of bowel-ischemia-related findings in adults. We report a case of COVID-19 in a healthy teenager who initially presented with isolated mesenteric adenopathy, typically a self-limited illness, which progressed to severe illness requiring intensive care before complete recovery. The boy tested negative for COVID-19 twice by polymerase chain reaction (PCR) from upper respiratory swabs before sputum PCR resulted positive. A high index of suspicion should be maintained for COVID-19 given the continued emergence of new manifestations of the disease.

Chronic airways infection with methicillin-resistant Staphylococcus aureus (MRSA) is associated with worse respiratory disease cystic fibrosis (CF) patients. Ceftaroline is a cephalosporin that inhibits the penicillin-binding protein (PBP2a) uniquely produced by MRSA. We analyzed 335 S. aureus isolates from CF sputum samples collected at three US centers between 2015-2018. Molecular relationships demonstrated that high-level resistance of preceding isolates to carbapenems were associated with subsequent isolation of ceftaroline resistant CF MRSA. In vitro evolution experiments showed that pre-exposure of CF MRSA to meropenem with further selection with ceftaroline implied mutations in mecA and additional mutations in pbp1 and pbp2, targets of carbapenems; no effects were achieved by other β-lactams. An in vivo pneumonia mouse model showed the potential therapeutic efficacy of ceftaroline/meropenem combination against ceftaroline-resistant CF MRSA infections. Thus, the present findings highlight risk factors and potential therapeutic strategies offering an opportunity to both prevent and address antibiotic resistance in this patient population.

The Type VI secretion system (T6SS) is a protein translocation nanomachine widespread among Gram-negative bacteria and used as a means to deliver effectors directly into target bacterial or eukaryotic cells. These effectors have a wide variety of functions within target cells that ultimately help the secreting cell gain a competitive fitness advantage. Here, we discuss the different ways in which these effectors can be delivered by the T6SS and the diverse mechanisms by which they exert their noxious action upon recipient cells. We also highlight the existence of roles for T6SS effectors beyond simply the killing of neighbouring cells., (© 2020 The Authors. Cellular Microbiology published by John Wiley & Sons Ltd.)

Objectives: This study examines the role of parental messages about body image in relation to body image dissatisfaction (BID) and depressive symptoms among Latinx college students. We assessed negative and positive messages about body image from mothers and fathers to examine the indirect effect of BID in explaining links from parental communication to depressive symptoms., Method: The sample included 198 Latinx college students in the southeastern United States (age range 18-25, 70% female). We used four mediation models, whereby parental comments were modeled to affect depressive symptoms through BID., Results: Results indicated that although there was no direct effect between parental messages and depressive symptoms, both negative maternal and paternal comments had indirect effects on depressive symptoms via BID., Conclusions: Parental messages about body image have significant implications for understanding the etiology of BID and concomitant depressive symptoms among Latinx college students. The findings highlight the important role of parental communication in Latinx student health and the need for future studies to better understand Latinx college students' interpretations of their parents' positive and negative comments. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Background/objective: Systemic lupus erythematosus (SLE) is an inflammatory, chronic, and multisystemic disease, which may be associated with a wide range of neuropsychiatric manifestations, including cognitive impairment. Cognitive evaluations based on screening tests might identify early SLE-related cognitive alterations. The aim of this study was to evaluate and to compare the efficacy of three screening tests (Montreal Cognitive Assessment [MoCA], Mini Mental State Examination [MMSE], Cognitive Symptom Inventory [CSI]) against the gold standard (neuropsychological battery), in order to identify the most efficient screening test for cognitive impairment in patients with SLE., Methods: This observational cross-sectional study recruited 44 patients, from August to December 2017, who were diagnosed with SLE according to the Systemic Lupus International Collaborating Clinics (SLICC) Criteria 2012, and had no medical or psychiatric comorbidities. The patients were evaluated using the MoCA, MMSE, CSI, and the gold standard. Spearman's correlation and area under the curve analysis were performed; p < 0.05 was considered significant., Results: The MoCA test showed the highest correspondence with the gold standard (AUC = 99.4%, p < 0.001), sensitivity (84%), and specificity (100%). This was followed by the MMSE (AUC = 92.6%, p < 0.001; sensitivity, 54.8%; specificity, 100%) and the CSI (AUC = 30.6%, p < 0.05; sensitivity, 54.8%; specificity, 30.76%)., Conclusion: The MoCA is a brief, easily applied screening test that is highly effective for detecting cognitive impairment in SLE patients. It could be useful in clinical follow-up as a tool for early detection of cognitive alterations.

Calcia-alumina binary compounds doped with rare earths and some transition metals cations show persistent luminescence from the visible to the infrared range. Specifically, the blue light can be obtained through the Eu 2+ activator center in a potential host, such as dodecacalcium hepta-aluminate (Ca 12 Al 14 O 33 ) and monocalcium aluminate (CaAl 2 O 4 ). By doping with Nd 3+ , the persistent luminescence can be substantially prolonged; for this reason, the Eu/Nd pair is a potential choice for developing long-lasting blue luminescence. Herein, the phase evolution of the calcia-alumina system via molten salt synthesis is reported as a function of the synthesis temperature and the atmospheric environment. The fraction of CaAl 2 O 4 phase increases when the temperature is higher. Synthesized microparticles of platelet-type morphology represent isolated nanostructured ceramic pieces. Under visible light, the particles are white. This indicates that the followed process solves the dark-gray coloring of phosphor when is synthesized in a reduced atmosphere at high temperature. As regards the synthesis mechanism, which is assisted by the molten flux, the dissolution-diffusion transport process is promoted at the surface of the alumina microparticles. In fact, the emission intensity can be modulated through the phase of the Eu-doped calcium-aluminate discrete platelets synthesized. Consequently, the photoluminescence intensity depends also on the oxidation state of the Eu ion. X-ray absorption near-edge structure and photoluminescence measurements corroborate the Eu reduction and the grain coarsening with the enhancement of the blue emission. The doped phosphors with Eu/Nd show a broad and strong absorption in the region of 320-400 nm and a broad emission band at around 440 nm when they are excited in this absorption range. From a broader perspective, our findings prove that the Ca 12 Al 14 O 33 and CaAl 2 O 4 phases open new opportunities for research into the design of blue long-lasting emitters for a wide range of fields from ceramic to optoelectronic materials., Competing Interests: The authors declare no conflict of interest.

Human cytomegalovirus (CMV) causes a wide array of disease to diverse populations of immune-compromised individuals. Thus, a more comprehensive understanding of how CMV enters numerous host cell types is necessary to further delineate the complex nature of CMV pathogenesis and to develop targeted therapeutics. To that end, we establish a vaccination strategy utilizing membrane vesicles derived from epithelial cells to generate a library of monoclonal antibodies (mAbs) targeting cell surface proteins in their native conformation. A high-throughput inhibition assay is employed to screen these antibodies for their ability to limit infection, and mAbs targeting CD46 are identified. In addition, a significant reduction of viral proliferation in CD46-KO epithelial cells confirms a role for CD46 function in viral dissemination. Further, we demonstrate a CD46-dependent entry pathway of virus infection in trophoblasts, but not in fibroblasts, highlighting the complexity of CMV entry and identifying CD46 as an entry factor in congenital infection.

The Mycobacterium tuberculosis lineage 4 strains CDC1551 and H37Rv develop tolerance to multiple antibiotics upon macrophage residence. To determine whether macrophage-induced tolerance is a general feature of clinical M. tuberculosis isolates, we assessed macrophage-induced drug tolerance in strains from lineages 1-3, representing the other predominant M. tuberculosis strains responsible for tuberculosis globally. All 3 lineages developed isoniazid tolerance. While lineage 1, 3, and 4 strains developed rifampin tolerance, lineage 2 Beijing strains did not. Their failure to develop tolerance may be explained by their harboring of a loss-of-function mutation in the Rv1258c efflux pump that is linked to macrophage-induced rifampicin tolerance., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Mycobacterium tuberculosis is the leading worldwide cause of death due to a single infectious agent. Existing anti-tuberculous therapies require long treatments and are complicated by multi-drug-resistant strains. Host-directed therapies have been proposed as an orthogonal approach, but few have moved into clinical trials. Here, we use the zebrafish- Mycobacterium marinum infection model as a whole-animal screening platform to identify FDA-approved, host-directed compounds. We identify multiple compounds that modulate host immunity to limit mycobacterial disease, including the inexpensive, safe, and widely used drug clemastine. We find that clemastine alters macrophage calcium transients through potentiation of the purinergic receptor P2RX7. Host-directed drug activity in zebrafish larvae depends on both P2RX7 and inflammasome signaling. Thus, targeted activation of a P2RX7 axis provides a novel strategy for enhanced control of mycobacterial infections. Using a novel explant model, we find that clemastine is also effective within the complex granulomas that are the hallmark of mycobacterial infection., Competing Interests: MM, DK, EW, RB, MC, CP, RH, DT No competing interests declared, (© 2019, Matty et al.)

The use of early-stage zebrafish for biomedical research spans early organogenesis to free-swimming larva. A key benefit of this model organism is that repeated assessments spanning several days can be performed of individual larvae within a single experiment, often in conjunction with administered drugs. However, the initiation of feeding, typically at 5 days postfertilization (dpf), can make serial assessments challenging. Therefore, delayed feeding would increase the utility of the model. To ask whether feeding could be delayed without adversely affecting larval growth and development up to 39 dpf, we systematically raised zebrafish and introduced feeding at 5 dpf or delayed initial feeding up to 9 dpf. We assessed survival into the juvenile stage (39 dpf) and anterior-posterior length at this age as proxies for growth and development. Delaying feeding initiation up to 8 dpf did not decrease baseline survival of greater than 90%; survival decreased to 66% only when delayed to 9 dpf. Larval length was no different under any of these conditions. Our findings define 9 dpf as the critical age before which larval zebrafish must be fed when raising to 39 dpf. The option to delay feeding to 8 dpf will broaden experimental applications for the zebrafish larval model.

In persistent luminescence materials, the SrO-Al 2 O 3 system has been mainly studied due to its chemical stability, higher photoluminescence response and longest green-afterglow times. Specifically, the research has focused on SrAl 2 O 4 doped with europium and dysprosium. SrAl 2 O 4 has two polymorphs: monoclinic polymorph (space group P 2 1 ) and hexagonal polymorph (space group P 6 3 22). Besides, the coexistence of these two phases, monoclinic and hexagonal, appears in almost all the results. However, it is not clear how this coexistence influences optical response. Some authors have reported that only the monoclinic structure exhibits luminescence properties, while another suggests that the hexagonal SrAl 2 O 4 polymorph has a higher emission efficiency than the monoclinic polymorph. Here we report a systematic evaluation of the effects of the stabilization of the hexagonal SrAl 2 O 4 polymorph. We show that an interrelationship between the hexagonal polymorph and phosphorescent properties is the linchpin for the development of good luminescence properties. Remarkably, the stabilization of the hexagonal SrAl 2 O 4 polymorph on the monoclinic-hexagonal polymorphic coexistence appears to be related to the preservation of the nanometric nature of the SrAl 2 O 4 -based system. Our results will help to understand the role of the hexagonal polymorph in the polymorphic coexistence on SrAl 2 O 4 -based systems and may facilitate the development of luminescent nanometric particles for the design and preparation of new light emitting materials., Competing Interests: The authors declare no competing financial interests., (This journal is © The Royal Society of Chemistry.)

The control of ferroelectric domain walls at the nanometric level leads to novel interfacial properties and functionalities. In particular, the comprehension of charged domain walls, CDWs, lies at the frontier of future nanoelectronic research. Whereas many of the effects have been demonstrated for ideal archetypes, such as single crystals, and/or thin films, a similar control of CDWs on polycrystalline ferroelectrics has not been achieved. Here, we unambiguously show the presence of charged domain walls on a lead-free (K,Na)NbO 3 polycrystalline system. The appearance of CDWs is observed in situ by confocal Raman microscopy and second harmonic generation microscopy. CDWs produce an internal strain gradient within each domain. Specifically, the anisotropic strain develops a crucial piece in the ferroelectric domain switching due to the coupling between the polarization of light and the ferroelectric polarization of the nanodomain in the (K,Na)NbO 3 ceramic. This effect leads to the tuning of the ferroelectric domain switching by means of the light polarization angle. Our results will help to understand the relevance of charged domain walls on the ferroelectric domain switching process and may facilitate the development of domain wall nanoelectronics by remote light control utilizing polycrystalline ferroelectrics.

B7H6, an endogenous ligand expressed on tumor cell surfaces, triggers NKp30-mediated activation of human NK cells. In contrast, the release of soluble B7H6 has been proposed as a novel mechanism by which tumors might evade NK cell-mediated recognition. Since NK cells are critical for the maintenance of early pregnancy, it is not illogical that soluble B7H6 might also be an important factor in directing NK cell activity during normal pregnancy. Thus, this study was focused on the characterization of soluble B7H6 during the development of normal pregnancy. Serum samples were obtained from healthy pregnant women who were experiencing their second pregnancies (n=36). Additionally, 17 of these pregnant participants were longitudinally studied for the presence of B7H6 during their second and third trimesters. Age-matched healthy non-pregnant women served as controls (n=30). The presence of soluble B7H6 was revealed by Western blotting. A further characterization was performed using an immunoproteomic approach based on 2DE-Western blotting combined with MALDI-MS. The results show that sera from all pregnant women were characterized by the presence of two novel isoforms of B7H6, both with lower MW than the reported of 51kDa. These isoforms were either a heavy (∼37kDa) or a light isoform (∼30kDa) and were mutually exclusive. N-glycosylation did not completely explain the different molecular weights exhibited by the two isoforms, as was demonstrated by enzymatic deglycosylation with PNGase F. The confirmation of the identity and molecular mass of each isoform indicates that B7H6, while maintaining the C- and N-termini, is most likely released during pregnancy by a mechanism distinct from proteolytic cleavage. We found that both isoforms, but mainly the heavier B7H6, were released via exosomes; and that the lighter isoform was also released in an exosome-free manner that was not observed in the heavy isoform samples. In conclusion, we find that soluble B7H6 is constitutively expressed during pregnancy and that, moreover, the soluble B7H6 is present in two new isoforms, which are released by exosomal and exosome-free mechanisms., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Interactions between tumor cells and tumor-associated macrophages play critical roles in the initiation of tumor cell motility. To capture the cellular interactions of the tumor microenvironment with high-resolution imaging, we directly visualized tumor cells and their interactions with macrophages in zebrafish. Live imaging in zebrafish revealed that macrophages are dynamic, yet maintain sustained contact with tumor cells. In addition, the recruitment of macrophages to tumor cells promotes tumor cell dissemination. Using a Cre/LoxP strategy, we found that macrophages transfer cytoplasm to tumor cells in zebrafish and mouse models. Remarkably, macrophage cytoplasmic transfer correlated with melanoma cell dissemination. We further found that macrophages transfer cytoplasm to tumor cells upon cell contact in vitro. Thus, we present a model in which macrophage/tumor cell contact allows for the transfer of cytoplasmic molecules from macrophages to tumor cells corresponding to increased tumor cell motility and dissemination., (Published by Elsevier Inc.)

The aim of this study was to analyze the impact of disease duration on carotid to femoral pulse wave velocity (cfPWV) in rheumatoid arthritis (RA) patients without either known traditional cardiovascular risk factors or previous comorbidities.Patients with RA diagnosis attending the rheumatology outpatient clinic of Hospital Civil Juan I. Menchaca, Guadalajara, Mexico, were analyzed. A total of 106 RA patients without known traditional cardiovascular risk factors were selected. All subjects were evaluated for RA disease duration, RA disease activity score on 28 joints (DAS28), serum lipids, rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) antibodies. Arterial stiffness was measured as cfPWV by noninvasive tonometry. A multivariate regression model was used to analyze the contribution of RA disease duration and age on cfPWV. cfPWV was positively correlated with age (r = 0.450, P < .001), RA disease duration (r = 0.340, P < .001), total cholesterol (r = 0.312, P = .002), and low density lipoprotein (LDL-c) cholesterol (r = 0.268, P = .012). Patients with a RA disease duration ≥10 years exhibited significantly increased cfPWV compared with patients with disease duration <2 years (8.4 ± 1.8 vs 7.0 ± 0.8) and ≥2 to <10 years (8.4 ± 1.8 vs 7.8 ± 1.3), respectively. Age, RA disease duration, and triglycerides were predictors of cfPWV in multivariate analyses. According to the β-coefficients, each year of disease duration (β = 0.072) had a greater impact on cfPWV than age (β = 0.054).Each year of life with RA contributes to a higher rate of vascular aging or stiffening than a year of life without RA. The cumulative damage provided by RA was most pronounced in patients with disease duration ≥10 years.

Intensive research has been focused on the synthesis of long-lasting SrAl 2 O 4 :EuDy in luminescent materials field. Traditionally, SrAl 2 O 4 :EuDy is synthesized in bulk form by solid state. However, their development remains restrained due to this technique is not compatible with large-scale production, sustainability and nanometer-scale requirements. Despite nano-range particles have been obtained by chemical routes, photoluminescence response decreases and application became unpractical. It remains a challenge to synthesize nonrare-earth (RE) phosphors with high photoluminescence. One major challenge for the luminescent materials community is to devise methods to deliver innovative, sustainable and cost effective solutions for the reduction of RE because of the lack of RE availability. Here, we suggest a solution based on molten salts, obtaining nanosheets or micro/nanostructured SrAl 2 O 4 :Eu, Dy particles with core-shell structure, employing only 50% of standard amounts of RE. Core-size and shell thickness and crystallinity can be tuned by post-thermal treatment, through which can be modulated the Eu +2 fraction. We find that our methodology leads the functional features of the analogous micron counterpart. These results can be considered a great achievement to scale-up the process. Besides, the harmful collateral effect of nanotechnology must be addressed by using new safe by design core-shell nanostructures.

Human cytomegalovirus is a ubiquitous β-herpesvirus that infects many different cell types through an initial binding to cell surface receptors followed by a fusion event at the cell membrane or endocytic vesicle. A recent high-throughput screen to identify compounds that block a step prior to viral gene expression identified podofilox as a potent and nontoxic inhibitor. Time-of-addition studies in combination with quantitative-PCR analysis demonstrated that podofilox limits an early step of virus entry at the cell surface. Podofilox was also able to drastically reduce infection by herpes simplex 1, an α-herpesvirus with a very similar entry process to CMV. Podofilox caused a reduced maximal plateau inhibition of infection by viruses with single step binding processes prior to fusion-like Newcastle disease virus, Sendai virus, and influenza A virus or viruses that enter via endocytosis like vesicular stomatitis virus and a clinical-like strain of CMV. These results indicate that microtubules appear to be participating in the post-binding step of virus entry including the pre- and post-penetration events. Modulation of the plasma membrane is required to promote virus entry for herpesviruses, and that podofilox, unlike colchicine or nocodazole, is able to preferentially target microtubule networks at the plasma membrane., Competing Interests: The authors declare no conflict of interest.

Objectives: This study aims to evaluate the association of hearing impairment with carotid intima-media thickness and subclinical atherosclerosis in rheumatoid arthritis (RA) patients., Patients and Methods: A total of 41 RA patients (2 males, 39 females; mean age 46.5±10.2 years; range 20 to 63 years) with no known traditional cardiovascular risk factors were included. Routine clinical and laboratory assessments for RA patients were performed. Pure tone air (250-8000 Hz) and bone conduction (250-6000 Hz) thresholds were obtained, tympanograms and impedance audiometry were conducted. Sensorineural hearing impairment was defined if the average thresholds were ≥25 decibels. Carotid intima-media thickness was assessed and classified with a cut-off point of 0.6 mm., Results: Thirteen patients (31.7%) had normal audition, while 28 (68.3%) had hearing impairment. Of these, 22 had bilateral sensorineural hearing impairment. Four patients had conductive hearing impairment (right in three patients and left in one patient). Patients with sensorineural hearing impairment had increased carotid intima-media thickness in the media segment of carotid common artery compared to patients with normal hearing (right ear p=0.007; left ear p=0.075). Thickening of the carotid intima-media thickness was associated with sensorineural hearing impairment in RA patients., Conclusion: Rheumatoid arthritis patients should be evaluated by carotid intima-media thickness as a possible contributing factor of hearing impairment in patients without cardiovascular risk factors., Competing Interests: Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

The prototypic betaherpesvirus human cytomegalovirus (CMV) establishes life-long persistence within its human host. While benign in healthy individuals, CMV poses a significant threat to the immune compromised, including transplant recipients and neonates. The CMV glycoprotein complex gH/gL/gO mediates infection of fibroblasts, and together with the gH/gL/UL128/130/131 a pentameric complex permits infection of epithelial, endothethial, and myeloid cells. Given the central role of the gH/gL complex during infection, we were interested in studying cellular trafficking of the gH/gL complex through generation of human cells that stably express gH and gL. When expressed alone, CMV gH and gL were degraded through the ER-associated degradation (ERAD) pathway. However, co-expression of these proteins stabilized the polypeptides and enhanced their cell-surface expression. To further define regulatory factors involved in gH/gL trafficking, a CMV gH chimera in which the gH transmembrane and cytoplasmic tail were replaced with that of human CD4 protein permitted cell surface gH expression in absence of gL. We thus demonstrate the ability of distinct cellular processes to regulate the trafficking of viral glycoproteins. Collectively, the data provide insight into the processing and trafficking requirements of CMV envelope protein complexes and provide an example of the co-opting of cellular processes by CMV.

Until now, lead zirconate titanate (PZT) based ceramics are the most widely used in piezoelectric devices. However, the use of lead is being avoided due to its toxicity and environmental risks. Indeed, the attention in piezoelectric devices has been moved to lead-free ceramics, especially on (K,Na)NbO3-based materials, due to growing environmental concerns. Here we report a systematic evaluation of the effects of the compositional modifications induced by replacement of the B-sites with Sb(5+) ions in 0.96[(K0.48Na0.52)0.95Li0.05Nb1-xSbxO3]-0.04[BaZrO3] lead-free piezoceramics. We show that this compositional design is the driving force for the development of the high piezoelectric properties. So, we find that this phenomenon can be explained by the stabilization of a Rhombohedral-Tetragonal (R-T) phase boundary close to room temperature, that facilities the polarization process of the system and exhibits a significantly high piezoelectric response with a d33 value as high as ∼400 pC/N, which is comparable to part soft PZTs. As a result, we believe that the general strategy and design principles described in this study open the possibility of obtaining (K,Na)NbO3-based lead-free ceramics with enhanced properties, expanding their application range.