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It is estimated that nearly five billion people do not have access to surgical care. Approximately 94% of individuals in low- and middle-income countries (LMICs) lack access to surgery in comparison to 14.9% in high-income countries (HICs). There are several urologic conditions requiring surgical intervention that are not treated because of the limited number of expert urologists in LMICs. Telesurgery is a concept that connects patients and surgeons in different locations through the use of a robotic surgery system. In this review, we explain the origins of telesurgery as well as the benefits and obstacles to its global implementation. Telesurgery can reduce travel times and the dangers associated with traveling for surgical care in LMICs. Additionally, telesurgery allows patients in LMICs to gain access to expert urologists while also providing effective training to upcoming surgeons. However, LMICs require substantial investment to improve digital infrastructure that will support urologic telesurgery. There will also be ethical, legal, and policy considerations that will need to be resolved for safe and equitable urologic telesurgery to occur. There have been multiple successful applications of urologic telesurgery, suggesting that the technology for this to become routine is already available. The time for international collaboration must begin now to reduce global disparities in access to urologic surgery.

Activating the expression of host susceptibility (S) genes is one of the strategies plant pathogens employed to promote infection of their host. Here, the authors show that targeted methylation at the TAL20 effector binding element of the cassava SWEET10a gene lead to resistance to Xanthomonas phaseoli.

Cassava mosaic disease is caused by geminiviruses and suppresses cassava yields throughout the tropics. Here, the authors show that mutations in MePOLD1, encoding DNA polymerase δ subunit 1, co-segregate with CMD2, the major source of genetic resistance for this disease.

Abstract Background Methods to accurately quantify disease severity are fundamental to plant pathogen interaction studies. Commonly used methods include visual scoring of disease symptoms, tracking pathogen growth in planta over time, and various assays that detect plant defense responses. Several image-based methods for phenotyping of plant disease symptoms have also been developed. Each of these methods has different advantages and limitations which should be carefully considered when choosing an approach and interpreting the results. Results In this paper, we developed two image analysis methods and tested their ability to quantify different aspects of disease lesions in the cassava-Xanthomonas pathosystem. The first method uses ImageJ, an open-source platform widely used in the biological sciences. The second method is a few-shot support vector machine learning tool that uses a classifier file trained with five representative infected leaf images for lesion recognition. Cassava leaves were syringe infiltrated with wildtype Xanthomonas, a Xanthomonas mutant with decreased virulence, and mock treatments. Digital images of infected leaves were captured overtime using a Raspberry Pi camera. The image analysis methods were analyzed and compared for the ability to segment the lesion from the background and accurately capture and measure differences between the treatment types. Conclusions Both image analysis methods presented in this paper allow for accurate segmentation of disease lesions from the non-infected plant. Specifically, at 4-, 6-, and 9-days post inoculation (DPI), both methods provided quantitative differences in disease symptoms between different treatment types. Thus, either method could be applied to extract information about disease severity. Strengths and weaknesses of each approach are discussed.

Environmental variability poses a major challenge to any field study. Researchers attempt to mitigate this challenge through replication. Thus, the ability to detect experimental signals is determined by the degree of replication and the amount of environmental variation, noise, within the experimental system. A major source of noise in field studies comes from the natural heterogeneity of soil properties which create microtreatments throughout the field. In addition, the variation within different soil properties is often nonrandomly distributed across a field. We explore this challenge through a sorghum field trial dataset with accompanying plant, microbiome, and soil property data. Diverse sorghum genotypes and two watering regimes were applied in a split-plot design. We describe a process of identifying, estimating, and controlling for the effects of spatially distributed soil properties on plant traits and microbial communities using minimal degrees of freedom. Importantly, this process provides a method with which sources of environmental variation in field data can be identified and adjusted, improving our ability to resolve effects of interest and to quantify subtle phenotypes.

Abstract Background This study aims to describe the short-term reactogenicity of the AS03-adjuvanted H5N1 vaccine expressed through adverse events (AEs) and quality-adjusted life-day (QALD) scores. The AEs are likely to be short-term and therefore the quality of life (QoL) questionnaire, SF-36v2, was administered daily to record changes over seven days. A more sensitive application of this instrument should allow for a better understanding of short-term tolerability of adjuvanted vaccines. Methods Participants (N = 50) received a 2-dose vaccination schedule. Solicited (collected daily: days 0 to 7 [post dose 1] and 21 to 28 [post dose 2]) and unsolicited (collected weekly until day 21) AEs were collected via diary cards. The QoL questionnaires were completed daily (days 0–6) and weekly (days 0, 6, 21, 27) after dose one. Questionnaire data were transformed into SF-6D scores to report QALDs. It was hypothesized post-hoc that the QALD and daily AEs scores should correlate if discrete QoL-changes were captured. Results Pain (92%) and muscle ache (66%) were the most commonly reported solicited local and general AEs respectively, neither increased in intensity nor in frequency after dose 2. No safety concerns were identified during the study. A correlation between the daily AEs and QALD scores existed (correlation coefficient, − 0.97 (p

AbstractResearch on a few model plant–pathogen systems has benefitted from years of tool and resource development. This is not the case for the vast majority of economically and nutritionally important plants, creating a crop improvement bottleneck. Cassava bacterial blight (CBB), caused by Xanthomonas axonopodismanihotisXamManihot esculentain vivoSMeSWEET10aMeSWEET10a-GFP

Abstract High‐throughput phenotyping (HTP) has emerged as one of the most exciting and rapidly evolving spaces within plant science. The successful application of phenotyping technologies will facilitate increases in agricultural productivity. High‐throughput phenotyping research is interdisciplinary and may involve biologists, engineers, mathematicians, physicists, and computer scientists. Here we describe the need for additional interest in HTP and offer a primer for those looking to engage with the HTP community. This is a high‐level overview of HTP technologies and analysis methodologies, which highlights recent progress in applying HTP to foundational research, identification of biotic and abiotic stress, breeding and crop improvement, and commercial and production processes. We also point to the opportunities and challenges associated with incorporating HTP across food production to sustainably meet the current and future global food supply requirements.

The zig-zag model of host-pathogen interaction describes the relative strength of defense response across a spectrum of pathogen-induced plant phenotypes. A stronger defense response results in increased resistance. Here, we investigate the strength of pathogen virulence during disease and place these findings in the context of the zig-zag model. Xanthomonas vasicola pv. holcicola (Xvh) causes sorghum bacterial leaf streak. Despite being widespread, this disease has not been described in detail at the molecular level. We divided diverse sorghum genotypes into three groups based on disease symptoms: water-soaked lesions, red lesions, and resistance. Bacterial growth assays confirmed that these three phenotypes represent a range of resistance and susceptibility. To simultaneously reveal defense and virulence responses across the spectrum of disease phenotypes, we performed dual RNA-seq on Xvh-infected sorghum. Consistent with the zig-zag model, the expression of plant defense-related genes was strongest in the resistance interaction. Surprisingly, bacterial virulence genes related to the type III secretion system (T3SS) and type III effectors (T3Es) were also most highly expressed in the resistance interaction. This expression pattern was observed at multiple time points within the sorghum-Xvh pathosystem. Further, a similar expression pattern was observed in Arabidopsis infected with Pseudomonas syringae for effector-triggered immunity via AvrRps4 but not AvrRpt2. Specific metabolites were able to repress the Xvh virulence response in vitro and in planta suggesting a possible signaling mechanism. Taken together, these findings reveal multiple permutations of the continually evolving host-pathogen arms race from the perspective of host defense and pathogen virulence responses.

Size‐based selectivity for metal ions based on highly preorganized five‐membered chelate rings is discussed. Metal ion complexation by the tetra‐pyridyl ligand EBIP ((8,9‐dihydro‐diquino[8,7‐b:7′,8′‐j][1,10]phenanthroline) is investigated, Formation constants (log K1) are reported for EBIP with 28 metal ions in 50 % CH3OH/H2O (v/v). The shift in size‐selectivity toward large metal ions and against small metal is demonstrated. Log K1 for the EBIP complexes shows a steady increase from La(III) to Lu(III), with a strong local maximum at Sm(III), and strong local minimum at Gd(III). This difference in log K1 between Sm(III) and Gd(III) for the tetra‐pyridyls is shown to depend largely on the level of preorganization of the ligand, being at a maximum for EBIP and a minimum for quaterpyridine. Log K1 for the Y(III) complex is invariably lower than for the similarly‐sized Ho(III) for all ligands that contain any nitrogen donors. Lower log K values for Y(III) are due to stabilization of the Ln(III) complexes with nitrogen donors by participation of the 5d orbitals, and to a lesser extent the 4 f orbitals, of the Ln(III) ions in M−L bonding. A DFT analysis of selectivity of tetra‐pyridyls for metal ions shows that Y(III) complexes should be less stable than similarly‐sized Ho(III) complexes. [ABSTRACT FROM AUTHOR]

High-throughput phenotyping has emerged as a powerful method for studying plant biology. Large image-based datasets are generated and analyzed with automated image analysis pipelines. A major challenge associated with these analyses is variation in image quality that can inadvertently bias results. Images are made up of tuples of data called pixels, which consist of R, G, and B values, arranged in a grid. Many factors, for example image brightness, can influence the quality of the image that is captured. These factors alter the values of the pixels within images and consequently can bias the data and downstream analyses. Here, we provide an automated method to adjust an image-based dataset so that brightness, contrast, and color profile is standardized. The correction method is a collection of linear models that adjusts pixel tuples based on a reference panel of colors. We apply this technique to a set of images taken in a high-throughput imaging facility and successfully detect variance within the image dataset. In this case, variation resulted from temperature-dependent light intensity throughout the experiment. Using this correction method, we were able to standardize images throughout the dataset, and we show that this correction enhanced our ability to accurately quantify morphological measurements within each image. We implement this technique in a high-throughput pipeline available with this paper, and it is also implemented in PlantCV.

Cotton bacterial blight (CBB), an important disease of (Gossypium hirsutum) in the early 20th century, had been controlled by resistant germplasm for over half a century. Recently, CBB re-emerged as an agronomic problem in the United States. Here, we report analysis of cotton variety planting statistics that indicate a steady increase in the percentage of susceptible cotton varieties grown each year since 2009. Phylogenetic analysis revealed that strains from the current outbreak cluster with race 18 Xanthomonas citri pv. malvacearum (Xcm) strains. Illumina based draft genomes were generated for thirteen Xcm isolates and analyzed along with 4 previously published Xcm genomes. These genomes encode 24 conserved and nine variable type three effectors. Strains in the race 18 clade contain 3 to 5 more effectors than other Xcm strains. SMRT sequencing of two geographically and temporally diverse strains of Xcm yielded circular chromosomes and accompanying plasmids. These genomes encode eight and thirteen distinct transcription activator-like effector genes. RNA-sequencing revealed 52 genes induced within two cotton cultivars by both tested Xcm strains. This gene list includes a homeologous pair of genes, with homology to the known susceptibility gene, MLO. In contrast, the two strains of Xcm induce different clade III SWEET sugar transporters. Subsequent genome wide analysis revealed patterns in the overall expression of homeologous gene pairs in cotton after inoculation by Xcm. These data reveal important insights into the Xcm-G. hirsutum disease complex and strategies for future development of resistant cultivars.

The gene-for-gene concept has historically been applied to describe a specific resistance interaction wherein single genes from the host and the pathogen dictate the outcome. These interactions have been observed across the plant kingdom and all known plant microbial pathogens. In recent years, this concept has been extended to susceptibility phenotypes in the context of transcription activator-like (TAL) effectors that target SWEET sugar transporters. However, because this interaction has only been observed in rice, it was not clear whether the gene-for-gene susceptibility was unique to that system. Here, we show, through a combined systematic analysis of the TAL effector complement of Xanthomonas axonopodis pv. manihotis and RNA sequencing to identify targets in cassava, that TAL20Xam668 specifically induces the sugar transporter MeSWEET10a to promote virulence. Designer TAL effectors (dTALE) complement TAL20Xam668 mutant phenotypes, demonstrating that MeSWEET10a is a susceptibility gene in cassava. Sucrose uptake–deficient X. axonopodis pv. manihotis bacteria do not lose virulence, indicating that sucrose may be cleaved extracellularly and taken up as hexoses into X. axonopodis pv. manihotis. Together, our data suggest that pathogen hijacking of plant nutrients is not unique to rice blight but also plays a role in bacterial blight of the dicot cassava.

[This corrects the article DOI: 10.1371/journal.pgen.1006049.].

Systemic acquired resistance, mediated by the Arabidopsis NPR1 gene and the rice NH1 gene, confers broad-spectrum immunity to diverse pathogens. NPR1 and NH1 interact with TGA transcription factors to activate downstream defense genes. Despite the importance of this defense response, the signaling components downstream of NPR1/NH1 and TGA proteins are poorly defined. Here we report the identification of a rice mutant, snim1, which suppresses NH1-mediated immunity and demonstrate that two genes encoding previously uncharacterized cysteine-rich-receptor-like kinases (CRK6 and CRK10), complement the snim1 mutant phenotype. Silencing of CRK6 and CRK10 genes individually in the parental genetic background recreates the snim1 phenotype. We identified a rice mutant in the Kitaake genetic background with a frameshift mutation in crk10; this mutant also displays a compromised immune response highlighting the important role of crk10. We also show that elevated levels of NH1 expression lead to enhanced CRK10 expression and that the rice TGA2.1 protein binds to the CRK10 promoter. These experiments demonstrate a requirement for CRKs in NH1-mediated immunity and establish a molecular link between NH1 and induction of CRK10 expression.

Bacterial spot disease of pepper and tomato is caused by four distinct Xanthomonas species and is a severely limiting factor on fruit yield in these crops. The genetic diversity and the type III effector repertoires of a large sampling of field strains for this disease have yet to be explored on a genomic scale, limiting our understanding of pathogen evolution in an agricultural setting. Genomes of sixty-seven Xanthomonas euvesicatoria (Xe), Xanthomonas perforans (Xp), and Xanthomonas gardneri (Xg) strains isolated from diseased pepper and tomato fields in the southeastern and midwestern United States were sequenced in order to determine the genetic diversity in field strains. Type III effector repertoires were computationally predicted for each strain, and multiple methods of constructing phylogenies were employed to understand better the genetic relationship of strains in the collection. A division in the Xp population was detected based on core genome phylogeny, supporting a model whereby the host-range expansion of Xp field strains on pepper is due, in part, to a loss of the effector AvrBsT. Xp-host compatibility was further studied with the observation that a double deletion mutant of AvrBsT and XopQ in Xp experiences a host gain for Nicotiana benthamiana. Extensive sampling of field strains and an improved understanding of effector content will aid in efforts to design disease resistance strategies targeted against highly conserved core effectors.

Wheat bran (WB) from Triticum aestivum has many beneficial effects on human health. To the best of our knowledge, very little has been published about its ability to prevent pathogenic bacterial adhesion in the intestine. Here, a WB extract was fractionated using different strategies, and the obtained fractions were tested in different in vitro methodologies to evaluate their interference in the attachment of enterotoxigenic Escherichia coli (ETEC) K88 to intestinal porcine epithelial cells (IPEC-J2) with the aim of identifying the putative anti-adhesive molecules. It was found that a proteinaceous compound in the >300-kDa fraction mediates the recognition of ETEC K88 to IPEC-J2. Further fractionation of the >300-kDa sample by size-exclusion chromatography showed several proteins below 90 kDa, suggesting that the target protein belongs to a high-molecular-weight (MW) multi-component protein complex. The identification of some relevant excised bands was performed by mass spectrometry (MS) and mostly revealed the presence of various protease inhibitors (PIs) of low MW: Serpin-Z2B, Class II chitinase, endogenous alpha-amylase/subtilisin inhibitor and alpha-amylase/trypsin inhibitor CM3. Furthermore, an incubation of the WB extract with ETEC K88 allowed for the identification of a 7S storage protein globulin of wheat, Globulin 3 of 66 kDa, which may be one of the most firmly attached WB proteins to ETEC K88 cells. Further studies should be performed to gain an understanding of the molecular recognition of the blocking process that takes place. All gathered information can eventually pave the way for the development of novel anti-adhesion therapeutic agents to prevent bacterial pathogenesis.

Rice NH1 (NPR1 homolog 1) is a key mediator of innate immunity. In both plants and animals, the innate immune response is often accompanied by rapid cell death at the site of pathogen infection. Over-expression of NH1 in rice results in resistance to the bacterial pathogen, Xanthomonas oryzae pv. oryzae (Xoo), constitutive expression of defense related genes and enhanced benzothiadiazole (BTH)- mediated cell death. Here we describe a forward genetic screen that identified a suppressor of NH1-mediated lesion formation and resistance, snl6. Comparative genome hybridization and fine mapping rapidly identified the genomic location of the Snl6 gene. Snl6 is a member of the cinnamoyl-CoA reductase (CCR)-like gene family. We show that Snl6 is required for NH1-mediated resistance to Xoo. Further, we show that Snl6 is required for pathogenesis-related gene expression. In contrast to previously described CCR family members, disruption of Snl6 does not result in an obvious morphologic phenotype. Snl6 mutants have reduced lignin content and increased sugar extractability, an important trait for the production of cellulosic biofuels. These results suggest the existence of a conserved group of CCR-like genes involved in the defense response, and with the potential to alter lignin content without affecting development.

A study is carried out on the Zn(super II) complex of cyclen that acts as a Lewis acid. This complex has additional steric factors operating as compared to the Zn(super II) aqua ion and these steric factors prevent the thiourea ligands from binding to the complex in the lower energy eclipsed conformation.

Dissolved formaldehyde in aqueous samples was determined at submicromolar levels by derivatization with Nash's reagent followed by liquid chromatography. The method requires little sample preparation, and the chromatogram is simple even in the presence of other aldehydes and ketones. The isocratic HPLC analysis is rapid with a low limit of detection (0.1 [[micro]molar]) and a precision of 1% RSD at 150 [[micro]molar]. The derivative is stable for at least 3 days at room temperature. Accuracy of the method was verified by intercomparison with an alternate, completely independent method, which utilizes another derivatizing agent.

A laboratory experiment for undergraduate chemistry students in a quantitative analysis class offers exposure to three common techniques of chemical analysis. Students use an ion-exchange resin to determine the amount of potassium and sodium in an unknown solid sample. Atomic absorption spectrophotometry is used to find the sodium concentration of the sample. The potassium concentration can be determined from the sodium concentration. Ion chromatography is used to determine the chloride concentration of the sample.

The voltametric and crystallographic study of complexes of Cd(II) with the crown ethers 12-crown-4, 15-crown-5, and 18-crown 6 is reported. Cd(II) forms stable complexes with the crown ethers 12-crown-4, 15-crown-5, and 18-crown 6, with a remarkable ability of the Cd(II) to bind strongly to these crowns of very different sizes.

Wheat bran (WB) from Triticum aestivum has many beneficial effects on human health. To the best of our knowledge, very little has been published about its ability to prevent pathogenic bacterial adhesion in the intestine. Here, a WB extract was fractionated using different strategies, and the obtained fractions were tested in different in vitro methodologies to evaluate their interference in the attachment of enterotoxigenic Escherichia coli (ETEC) K88 to intestinal porcine epithelial cells (IPEC-J2) with the aim of identifying the putative anti-adhesive molecules. It was found that a proteinaceous compound in the >300-kDa fraction mediates the recognition of ETEC K88 to IPEC-J2. Further fractionation of the >300-kDa sample by size-exclusion chromatography showed several proteins below 90 kDa, suggesting that the target protein belongs to a high-molecular-weight (MW) multi-component protein complex. The identification of some relevant excised bands was performed by mass spectrometry (MS) and mostly revealed the presence of various protease inhibitors (PIs) of low MW: Serpin-Z2B, Class II chitinase, endogenous alpha-amylase/subtilisin inhibitor and alpha-amylase/trypsin inhibitor CM3. Furthermore, an incubation of the WB extract with ETEC K88 allowed for the identification of a 7S storage protein globulin of wheat, Globulin 3 of 66 kDa, which may be one of the most firmly attached WB proteins to ETEC K88 cells. Further studies should be performed to gain an understanding of the molecular recognition of the blocking process that takes place. All gathered information can eventually pave the way for the development of novel anti-adhesion therapeutic agents to prevent bacterial pathogenesis. [ABSTRACT FROM AUTHOR]

Some plant extracts, have been demonstrated to interfere with the microbial metabolism of several pathogenic bacteria. Within this antimicrobial properties it has been described the potential to inhibit or destroy biofilms or to interfere in quorum-sensing ( QS) systems. However, to our knowledge, no study exploring this potential of wheat-bran ( WB) has been published. The purpose of the present study is to evaluate the anti-biofilm activity of WB against a cow mastitis strain of S taphylococcus aureus and also its possible interference with bacterial QS systems. The potential of inhibition and destruction of the biofilm was studied by different in vitro assays. Also, we tested the ability of WB to interfere in bacterial QS by degrading acyl-homoserine lactones ( AHL) as one of the most studied QS signal molecules for Gram-negative bacteria. The soluble extract of WB at 0.5% showed anti-biofilm activity, inhibiting biofilm formation and also destroying it. Similarly, the > 300 kDa fraction from WB had significant anti-biofilm activity in both in vitro assays. The WB also showed a potential to interfere with bacterial QS systems, as it was demonstrated to contain certain lactonase activity able to reduce AHL concentration in the medium. The present study reveals two additional beneficial properties of WB extract never explored before, which may be related to the presence of defence compounds in the plant extract able to interfere with microbial biofilms and also QS systems. [ABSTRACT FROM AUTHOR]

A differential pulse voltammetric study of complexes of Cd(Il) and Pb(ll) with crown ethers is reported. Measured log K1 values for Cd(Il) with 18-crown-6 (1,4,7,10,13,16-hexaoxacyclooctadecane), 15-crown-5 (1,4,7,10,13pentaoxacyclopentadecane), and 12-crown-4 (1,4,7,10-tetraoxacyclododecane) are respectively 2.53 (±0.06), 1.97 (±0.07), and 1.72 (±0.08) and for Pb(ll) with 18-crown-6 is 4.17 (±0.03), all at 25 °C in 0.1 M LiNO3. Cd(Il) is smaller than is usually associated with strong bonding with crown ethers. The high log K1 values for Cd2+ with crown ethers found here are discussed in terms of distortion of Cd(Il) by relativistic effects. The resulting plasticity of the coordination geometry of the Cd(Il) ion allows it to meet the metal ion size requirements of all the crown ethers, allowing high log K1 values to occur. Crystal structures for [Cd(bz-18-crown-6)(SCN)2] (1) (bz-18-crown-6 = benzo-1,4,7,10,13,16-hexaoxacyclooctadecane) and [K(18-crown-6)][Cd(SCN)3] (2) are reported. 1 was triclinic, space group P1, a = 8.5413(2), b = 10.0389(2), and c = 13.4644(2) Å, α = 94.424(1), β = 102.286(1), and γ = 93.236(1)°, Z = 2, and final R = 0.023. 2 was orthorhombic, space group Crnc21, a = 14.7309(3), b = 15.1647(3), and c = 10.6154(2) Å, Z= 4, and final R = 0.020. In 1, the Cd occupies the cavity of the bz-18crown-6 with long average Cd-O bond lengths of 2.65 Å and is N-bonded to the thiocyanates with short average Cd-N bonds of 2.12 Å. In [Cd(bz-18-crown-6)(SCN)2], the linear coordination involving the Cd and the two N-bonded thiocyanate groups in 1 is discussed in terms of the role of relativistic effects in the tendency to linear coordination geometry in group 12 metal ions. In 2 Cd forms a polymeric structure involving thiocyanate bridges between Cd atoms and K+ occupies the cavity of the crown ether. 2 highlights the fact that cadmium is almost never S-bonded to thiocyanate except in bridging thiocyanates. re of [Cd(benzo-18-crown-6)(NCS)2] and [K(18-crown-6)][Cd(SCN)3]. [ABSTRACT FROM AUTHOR]

The effects of local treatment with highly purified tannic acid (HPTA) on serum transaminase and alkaline phosphatase activity in burn patients were studied, retrospectively. Temporary elevations in the activity of gamma-glutamyl transferase (GGT), aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT) and alkaline phosphatase (AP) were observed in both HPTA-treated patients and their matched controls. No statistically significant difference was found between the two patient-groups with respect to the mean enzyme activities, calculated as the areas under the curve between 5 and 15 days post-burn (PBD). These results seem to indicate that HPTA does not cause hepatotoxicity, at least when applied to a burned area corresponding to approximately 10% of the total body surface. This is in agreement with the widespread and frequent use of HPTA in the food, cosmetic and pharmaceutical industries. [Copyright &y& Elsevier]

Inspired by the structure of tannic acid, first- to third-generation dendrimers containing two, four, and eight galloyl moieties were synthesized. Stability, antioxidant activity and collagen cross-linking activity of the natural product and its dendrimer analogues were compared. The experimental results indicate that polygalloyl dendrimers might be used as new lead compounds to improve the long-term healing characteristics of burn wounds. [Copyright &y& Elsevier]

Within the group of botanical products there is a large range of variation with regard to their properties. Some products are identical to foods while others come close to or are medicines. Botanical products are regulated differently within the different member states of the European Union (EU) and globally. They are regulated either as food or as medicinal products, and in the latter case often with simplified registration procedures. These differences are caused by differences in traditional use, in cultural and historical background, in scientific substantiation and in enforcement of current legislation. One may expect that in the future differences will remain, unless EU legislation is enacted with sufficient room for different approaches. The strengths and weaknesses of the different regulatory procedures have been reviewed and evaluated as well as the current methods for quality, efficacy and safety evaluation. Criteria to categorize botanical products have been defined, such that botanical products can be regulated under the current food and medicinal regulations. Furthermore, a decision tree has been developed as a tool to distinguish herbal medicinal products from botanical health products and vice versa, and to provide a stepwise framework for the assessment of safety and efficacy. [Copyright &y& Elsevier]

Background: Stuttering priapism is characterized by recurrent, self-limited episodes of penile erection lasting from a few minutes to a maximum of three hours, often resolving spontaneously. These episodes can occur with or without sexual stimulation. If not treated promptly and effectively, stuttering priapism can severely impact a patient's quality of life, leading to significant psychological distress and anxiety related to sexual performance. Although it has been associated with various hematological disorders and pharmacological treatments, many cases of stuttering priapism remain idiopathic, meaning they have no identifiable cause. Currently, no conclusive randomized clinical trials exist on the management of idiopathic stuttering priapism. This study aims to review the existing literature on the pathophysiology and management of idiopathic stuttering priapism and propose an algorithm to assist physicians in its evaluation and treatment., Results: A systematic literature review was conducted using the PubMed database, focusing on the terms "idiopathic," "stuttering," "ischemic," and "priapism." The search identified 23 relevant references published between 1991 and 2022. The selection and analysis of these studies adhered to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, and results were described qualitatively. Recent research into the effectiveness, sustainability, tolerability, and side effects of various treatments for idiopathic stuttering priapism has enhanced the understanding of its underlying molecular mechanisms. Various treatments, targeting different mechanisms, have been identified that can potentially reduce the frequency and severity of episodes and improve patient outcomes., Conclusion: Current research predominantly addresses the acute treatment of idiopathic stuttering priapism rather than strategies to alter the disease's overall course. The limited number of treatment reviews, case reports, and the low level of evidence available, combined with the absence of randomized clinical trials, prevent the establishment of a consensus on treatment protocols. As a result, idiopathic stuttering priapism remains under-recognized and under-treated. This review proposes a management framework to help clinicians access and apply the available literature effectively, minimizing the reliance on extensive case reports and review articles., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Ad26.RSV.preF is an adenovirus serotype 26 vector-based respiratory syncytial virus (RSV) vaccine encoding a prefusion conformation-stabilized RSV fusion protein (preF) that demonstrated robust humoral and cellular immunogenicity and showed promising efficacy in a human challenge study in younger adults. Addition of recombinant RSV preF protein might enhance RSV-specific humoral immune responses, especially in older populations., Methods: This randomized, double-blind, placebo-controlled, phase 1/2a study compared the safety and immunogenicity of Ad26.RSV.preF alone and varying doses of Ad26.RSV.preF-RSV preF protein combinations in adults aged ≥60 years. This report includes data from cohort 1 (initial safety, n = 64) and cohort 2 (regimen selection, n = 288). Primary immunogenicity and safety analyses were performed 28 days postvaccination (cohort 2) for regimen selection., Results: All vaccine regimens were well tolerated, with similar reactogenicity profiles among them. Combination regimens induced greater humoral immune responses (virus-neutralizing and preF-specific binding antibodies) and similar cellular ones (RSV-F-specific T cells) as compared with Ad26.RSV.preF alone. Vaccine-induced immune responses remained above baseline up to 1.5 years postvaccination., Conclusions: All Ad26.RSV.preF-based regimens were well tolerated. A combination regimen comprising Ad26.RSV.preF, which elicits strong humoral and cellular responses, and RSV preF protein, which increases humoral responses, was selected for further development. Clinical Trials Registration. NCT03502707., Competing Interests: Potential conflicts of interests. C. A. C and E. H. are former employees of Janssen Vaccines & Prevention B.V. A. R. B., L.v. d. F., R. v. H., B. C., and J. S. are employees of Janssen Vaccines & Prevention B.V. V. K. is an employee of Janssen Infectious Diseases. E. D. P. and E. O. are former employees of Janssen Infectious Diseases. S. B. reports no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: Family members of autistic individuals often provide support for their autistic relative throughout the lifespan which can lead to massive burden themselves. Reduced health-related Quality of Life (HRQoL) in family caregivers is assumed; however, only a handful studies on the HRQoL of family caregivers providing care to adult relatives exist as opposed to autistic children. Thus, the current study aimed to (i) investigate the current state of physical and mental HRQoL of family caregivers of autistic adults compared to the general population, and (ii) examine caregiver-related (e.g., age, subjective caregiver burden) and care recipient-related variables (e.g., symptom severity, utilization of formal services) explaining variance in the caregivers' HRQoL., Methods: N = 149 family caregivers completed a nationwide online survey, including the Short-Form Health Survey (SF-8) in order to assess the HRQoL. T-tests were used to compare the HRQoL of family caregivers with the general population. Bivariate correlational and multiple linear regression analyses were conducted in order to identify predictors explaining variance in family caregivers' HRQoL., Results: Family caregivers of autistic adults reported significantly lower physical ( M = 46.71, SD = 8.72, Cohen's d = 0.42) and mental HRQoL ( M = 40.15, SD = 11.28, Cohen's d = 1.35) compared to the general population. Multiple linear regression with the mental HRQoL as the outcome showed a significant model ( F (11, 95) = 5.53, p < .001, adj. R 2 = .32) with increased subjective burden explaining most of the variance in mental HRQoL ( ß = .32, GDW = .141, p < .001). Multiple linear regression analysis with the outcome physical HRQoL did not reveal a statistically significant model ( F (11,95) = 1.09, p = .38). However, bivariate analyses also showed a positive correlation with the subjective caregiver burden ( r = .20, p < .05)., Discussion: Findings highlight the need to consider HRQoL (and caregiver burden) of family caregivers of autistic adults in several healthcare settings to monitor a potential comprised health status in early stages, with the long-term goal to improve family caregivers' HRQoL., 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., (Copyright © 2023 Dückert, Bart, Gewohn, König, Schöttle, Konnopka, Rahlff, Erik, Vogeley, Schulz, David and Peth.)

Background: Chikungunya, a mosquito-borne viral disease caused by the chikungunya virus (CHIKV), causes a significant global health burden, and there is currently no approved vaccine to prevent chikungunya disease. In this study, the safety and immunogenicity of a CHIKV mRNA vaccine candidate (mRNA-1388) were evaluated in healthy participants in a CHIKV-nonendemic region., Methods: This phase 1, first-in-human, randomized, placebo-controlled, dose-ranging study enrolled healthy adults (ages 18-49 years) between July 2017 and March 2019 in the United States. Participants were randomly assigned (3:1) to receive 2 intramuscular injections 28 days apart with mRNA-1388 in 3 dose-level groups (25 μg, 50 μg, and 100 μg) or placebo and were followed for up to 1 year. Safety (unsolicited adverse events [AEs]), tolerability (local and systemic reactogenicity; solicited AEs), and immunogenicity (geometric mean titers [GMTs] of CHIKV neutralizing and binding antibodies) of mRNA-1388 versus placebo were evaluated., Results: Sixty participants were randomized and received ≥ 1 vaccination; 54 (90 %) completed the study. mRNA-1388 demonstrated favorable safety and reactogenicity profiles at all dose levels. Immunization with mRNA-1388 induced substantial and persistent humoral responses. Dose-dependent increases in neutralizing antibody titers were observed; GMTs (95 % confidence intervals [CIs]) at 28 days after dose 2 were 6.2 (5.1-7.6) for mRNA-1388 25 μg, 53.8 (26.8-108.1) for mRNA-1388 50 μg, 92.8 (43.6-197.6) for mRNA-1388 100 μg, and 5.0 (not estimable) for placebo. Persistent humoral responses were observed up to 1 year after vaccination and remained higher than placebo in the 2 higher mRNA-1388 dose groups. The development of CHIKV-binding antibodies followed a similar trend as that observed with neutralizing antibodies., Conclusions: mRNA-1388, the first mRNA vaccine against CHIKV, was well tolerated and elicited substantial and long-lasting neutralizing antibody responses in healthy adult participants in a nonendemic region., Clinicaltrials: gov: NCT03325075., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: A.A., C.A.S., C.K., H.Z., and L.P. are employees of Moderna, Inc., and may hold stock/stock options in the company. S.B., P.-G.J.B., T.B., and S.W. have no relevant or material financial interests that relate to the research described in this article., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Respiratory syncytial virus (RSV) can cause serious lower respiratory tract disease in older adults, but no licensed RSV vaccine currently exists. An adenovirus serotype 26 RSV vector encoding a prefusion F (preF) protein (Ad26.RSV.preF) in combination with RSV preF protein was previously shown to elicit humoral and cellular immunogenicity., Methods: We conducted a randomized, double-blind, placebo-controlled, phase 2b, proof-of-concept trial to evaluate the efficacy, immunogenicity, and safety of an Ad26.RSV.preF-RSV preF protein vaccine. Adults who were 65 years of age or older were randomly assigned in a 1:1 ratio to receive vaccine or placebo. The primary end point was the first occurrence of RSV-mediated lower respiratory tract disease that met one of three case definitions: three or more symptoms of lower respiratory tract infection (definition 1), two or more symptoms of lower respiratory tract infection (definition 2), and either two or more symptoms of lower respiratory tract infection or one or more symptoms of lower respiratory tract infection plus at least one systemic symptom (definition 3)., Results: Overall, 5782 participants were enrolled and received an injection. RSV-mediated lower respiratory tract disease meeting case definitions 1, 2, and 3 occurred in 6, 10, and 13 vaccine recipients and in 30, 40, and 43 placebo recipients, respectively. Vaccine efficacy was 80.0% (94.2% confidence interval [CI], 52.2 to 92.9), 75.0% (94.2% CI, 50.1 to 88.5), and 69.8% (94.2% CI, 43.7 to 84.7) for case definitions 1, 2, and 3, respectively. After vaccination, RSV A2 neutralizing antibody titers increased by a factor of 12.1 from baseline to day 15, a finding consistent with other immunogenicity measures. Percentages of participants with solicited local and systemic adverse events were higher in the vaccine group than in the placebo group (local, 37.9% vs. 8.4%; systemic, 41.4% vs. 16.4%); most adverse events were mild to moderate in severity. The frequency of serious adverse events was similar in the vaccine group and the placebo group (4.6% and 4.7%, respectively)., Conclusions: In adults 65 years of age or older, Ad26.RSV.preF-RSV preF protein vaccine was immunogenic and prevented RSV-mediated lower respiratory tract disease. (Funded by Janssen Vaccines and Prevention; CYPRESS ClinicalTrials.gov number, NCT03982199.)., (Copyright © 2023 Massachusetts Medical Society.)

Hypertriglyceridemia (HTG) is a prevalent medical condition in patients with cardiometabolic risk factors and is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD), if left undiagnosed and undertreated. Current guidelines identify HTG as a risk-enhancing factor and, as a result, recommend clinical evaluation and lifestyle-based interventions to address potential secondary causes of elevated triglyceride (TG) levels. For individuals with mild to moderate HTG at risk of ASCVD, statin therapy alone or in combination with other lipid-lowering medications known to decrease ASCVD risk are guideline-endorsed. In addition to lifestyle modifications, patients with severe HTG at risk of acute pancreatitis may benefit from fibrates, mixed formulation omega-3 fatty acids, and niacin; however, evidence does not support their use for ASCVD risk reduction in the contemporary statin era. Novel therapeutics including those that target apoC-III and ANGPTL3 have shown to be safe, well-tolerated, and effective for lowering TG levels. Given the growing burden of cardiometabolic disease and risk factors, public health and health policy strategies are urgently needed to enhance access to effective pharmacotherapies, affordable and nutritious food options, and timely health care services.

Lepidopteran species can be both pests and also beneficial pollinators for agricultural crops. However, despite these important roles, the effects of pesticides on this diverse taxa are relatively understudied. To facilitate the assessment of pesticides and other chemical hazards on this taxa, we present a novel bioassay capable of testing chemical sensitivity to lepidopteran larvae through dietary exposure. We used Mamestra brassicae caterpillars as a model lepidopteran and tested their sensitivity for the organophosphate insecticide chlorpyrifos. We exposed larvae to an artificial diet spiked with chlorpyrifos and monitored survival over time, as well as weight change over a 96-hour exposure period. To test the repeatability and reliability of the developed bioassay, the experiment was repeated three times. The survival in time data collected enabled analysis with the General Unified Threshold of Survival (GUTS) model, recently recognized by EFSA as a ready-to-use tool for regulatory purposes. The GUTS modelling was used to derive a set of relevant toxicokinetic and toxicodynamic parameters relating to the larval response to exposure over time. We found that across the three repeats studies there was no more than a threefold difference in LC₅₀ values (13.1, 18.7 and 8.1 mg/Kg) at 48 h and fourfold difference at 96 h, highlighting the repeatability of the bioassay. We also highlighted the potential of the method to observe sub-lethal effects such as changes in weight. Finally, we discuss the applications of this new bioassay method to chemical risk assessments and its potential for use in other scenarios, such as mixture or pulsed exposure testing., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:David Spurgeon reports financial support was provided by UK Research and Innovation. Claire Badder reports financial support was provided by UKRI., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)