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Abstract Schistosomiasis persists in Asian regions despite aggressive elimination measures. To identify factors enabling continued parasite transmission, we performed reduced representation genome sequencing on Schistosoma japonicum miracidia collected across multiple years from transmission hotspots in Sichuan, China. We discovered strong geographic structure, suggesting that local, rather than imported, reservoirs are key sources of persistent infections in the region. At the village level, parasites collected after referral for praziquantel treatment are closely related to local pre-treatment populations. Schistosomes within villages are also highly related, suggesting that only a few parasites from a limited number of hosts drive re-infection. The close familial relationships among miracidia from different human hosts also implicate short transmission routes among humans. At the individual host level, genetic evidence indicates that multiple humans retained infections following referral for treatment. Our findings suggest that end-game schistosomiasis control measures should focus on completely extirpating local parasite reservoirs and confirming successful treatment of infected human hosts.

The Gulf of Mexico pink shrimp, Farfantepenaeus duorarum, supports large fisheries in the United States and Mexico, with nearly 7,000 tons harvested from the region in 2016. Given the commercial importance of this species, management is critical: in 1997, the southern Gulf of Mexico pink shrimp fishery was declared collapsed and mitigation strategies went into effect, with recovery efforts lasting over a decade. Fisheries management can be informed and improved through a better understanding of how factors associated with early life history impact genetic diversity and population structure in the recruited population. Farfantepenaeus duorarum are short-lived, but highly fecund, and display high variability in recruitment patterns. To date, modeling the impacts of ecological, physical, and behavioral factors on juvenile settlement has focused on recruitment of larval individuals of F. duorarum to nursery grounds in Florida Bay. Here, we articulate testable hypotheses stemming from a recent model of larval transport and evaluate support for each with a population genomics approach, generating reduced representation library sequencing data for F. duorarum collected from seven regions around the Florida Peninsula. Our research represents the first and most molecular data-rich study of population structure in F. duorarum in the Gulf and reveals evidence of a differentiated population in the Dry Tortugas. Our approach largely validates a model of larval transport, allowing us to make management-informative inferences about the impacts of spawning location and recruitment patterns on intraspecific genetic diversity. Such inferences improve our understanding of the roles of non-genetic factors in generating and maintaining genetic diversity in a commercially important penaeid shrimp species.

Genomic approaches hold great promise for resolving unanswered questions about transmission patterns and responses to control efforts for schistosomiasis and other neglected tropical diseases. However, the cost of generating genomic data and the challenges associated with obtaining sufficient DNA from individual schistosome larvae (miracidia) from mammalian hosts have limited the application of genomic data for studying schistosomes and other complex macroparasites. Here, we demonstrate the feasibility of utilizing whole genome amplification and sequencing (WGS) to analyze individual archival miracidia. As an example, we sequenced whole genomes of 22 miracidia from 11 human hosts representing two villages in rural Sichuan, China, and used these data to evaluate patterns of relatedness and genetic diversity. We also down-sampled our dataset to test how lower coverage sequencing could increase the cost effectiveness of WGS while maintaining power to accurately infer relatedness. Collectively, our results illustrate that population-level WGS datasets are attainable for individual miracidia and represent a powerful tool for ultimately providing insight into overall genetic diversity, parasite relatedness, and transmission patterns for better design and evaluation of disease control efforts.

The Gulf of Mexico experiences frequent perturbations, both natural and anthropogenic. To better understand the impacts of these events, we must inventory natural variability within the ecosystem, communities, species, and populations, and contextualize these findings in relation to physical features. Here, we present an integrated study of comparative population genomics and biophysical oceanography. Targeting three species of mesopelagic shrimp common to the Gulf of Mexico midwater (Acanthephyra purpurea, Systellaspis debilis, and Robustosergia robusta), we analyzed genetic diversity and population connectivity as proxies for species health and resilience, respectively. We also simulated a range of vertical migratory behaviors for the shrimp to infer the relationship between diel vertical migration and horizontal transmission between the Gulf of Mexico and the greater Atlantic Ocean. This study aims to establish biological baselines and characterize these values in terms of the prevailing oceanographic feature of the midwater: the Gulf Loop Current. Generally, the oplophorid species (A. purpurea and S. debilis) exhibit lower genetic diversity and higher interpopulation homogeneity compared to the sergestid (R. robusta). Biophysical simulations suggest the differences in vertical migratory regimes between these two groups have important implications for horizontal transport out of the Gulf of Mexico. Because of the difference in vertical migration patterns, access to the Gulf Loop Current varies across taxa and impacts inter-basin migration. Our findings suggest a negative correlation between surface abundance and genetic diversity in these three shrimp species. We hypothesize that this correlation may be due to the relationships between surface abundance and access to the fastest moving waters of the Gulf Loop Current.

Helicoverpa armigera (Hübner) is one of the most important agricultural pests in the world. This historically Old World species was first reported in Brazil in 2013 and has since spread throughout much of South America and into the Caribbean. Throughout North America, H. armigera surveys are ongoing to detect any incursions. Each trap is capable of capturing hundreds of native Helicoverpa zea (Boddie). The two species cannot be separated without genitalic dissection or molecular methods. A ddPCR assay is currently used to screen large trap samples, but this equipment is relatively uncommon and expensive. Here, we optimized a newly designed assay for accurate and repeatable detection of H. armigera in bulk samples across both ddPCR and less costly, and more common, real-time PCR methods. Improvements over previously designed assays were sought through multiple means. Our results suggest bulk real-time PCR assays can be improved through changes in DNA extraction and purification, so that real-time PCR can be substituted for ddPCR in screening projects. While ddPCR remains a more sensitive method for detection of H. armigera in bulk samples, the improvements in assay design, DNA extraction, and purification presented here also enhance assay performance over previous protocols.

Abstract Thermal bleaching, or the loss of symbiotic algae that provide most energetic resources for the coral host, is an increasing threat to reefs worldwide and is projected to worsen with climate change. While bleaching is a well-recognized threat, the impact on the process of reproduction in bleaching survivors is not well resolved, despite being central to coral resilience. Montipora capitata can survive bleaching while completing a full gametogenic cycle, offering an ideal system to study gametogenic resilience and physiological tradeoffs. We experimentally bleached fragments of M. capitata colonies and followed their gametogenesis and physiological responses for 10 months (six time points). All bleached colonies produced gametes at the same time as controls, suggesting that reproductive processes were energetically prioritized. However, proteomic analysis revealed tradeoffs and delays in activating key physiological processes earlier in gametogenesis in areas such as skeletal growth and reproductive hormone synthesis. Tradeoffs during the gametogenic cycle, likely a direct response to thermal bleaching, resulted in smaller oocytes from bleached colonies, potentially indicating decreased transfer of parental resources to gametes. While gametogenesis is likely to continue in this species, it is unknown how the fecundity, synchrony of spawning, viability and success of future offspring may be impacted by future bleaching events.

Protein arginine methyl transferase 5 (PRMT5) is a signaling protein and histone modifying enzyme that is important in many cellular processes, including regulation of eukaryotic gene transcription. Reported here is a 3.7 Å structure of PRMT5, solved in complex with regulatory binding subunit MEP50 (methylosome associated protein 50, WDR77, p44), by single particle (SP) cryo-Electron Microscopy (cryo-EM) using micrographs of particles that are visibly crowded and aggregated. Despite suboptimal micrograph appearance, this cryo-EM structure is in good agreement with previously reported crystal structures of the complex, which revealed a 450 kDa hetero-octameric assembly having internal D2 symmetry. The catalytic PRMT5 subunits form a core tetramer and the MEP50 subunits are arranged peripherally in complex with the PRMT5 N-terminal domain. The cryo-EM reconstruction shows good side chain definition and shows a well-resolved peak for a bound dehydrosinefungin inhibitor molecule. These results demonstrate the applicability of cryo-EM in determining structures of human protein complexes of biomedical significance and suggests cryo-EM could be further utilized to understand PRMT5 interactions with other biologically important binding proteins and ligands.

Moths in the genus Helicoverpa are some of the most important agricultural pests in the world. Two species, H. armigera (Hübner) and H. zea (Boddie), cause the majority of damage to crops and millions of dollars are spent annually on control of these pests. The recent introduction of H. armigera into the New World has prompted extensive survey efforts for this species in the United States. Surveys are conducted using bucket traps baited with H. armigera pheromone, and, because the same pheromone compounds attract both species, these traps often capture large numbers of the native H. zea. Adult H. armigera and H. zea are very similar and can only be separated morphologically by minor differences in the genitalia. Thus, a time consuming genitalic dissection by a trained specialist is necessary to reliably identify either species, and every specimen must be dissected. Several molecular methods are available for differentiating and identifying H. armigera and H. zea, including two recently developed rapid protocols using real-time PCR. However, none of the published methods are capable of screening specimens in large batches. Here we detail a droplet digital PCR (ddPCR) assay that is capable of detecting a single H. armigera in a background of up to 999 H. zea. The assay has been tested using bulk extractions of 1,000 legs from actual trap samples and is effective even when using poor quality samples. This study provides an efficient, rapid, reproducible, and scalable method for processing H. armigera survey trap samples in the U.S. and demonstrates the potential for applying ddPCR technology to screen and diagnose invasive species.

Dynamics of three MET antibody constructs (IgG1, IgG2, and IgG4) and the IgG4-MET antigen complex was investigated by creating their atomic models with an integrative experimental and computational approach. In particular, we used two-dimensional (2D) Electron Microscopy (EM) images, image class averaging, homology modeling, Rapidly exploring Random Tree (RRT) structure sampling, and fitting of models to images, to find the relative orientations of antibody domains that are consistent with the EM images. We revealed that the conformational preferences of the constructs depend on the extent of the hinge flexibility. We also quantified how the MET antigen impacts on the conformational dynamics of IgG4. These observations allow to create testable hypothesis to investigate MET biology. Our protocol may also help describe structural diversity of other antigen systems at approximately 5 Å precision, as quantified by Root-Mean-Square Deviation (RMSD) among good-scoring models.

The Russian wheat aphid, Diuraphis noxia, an invasive phytotoxic pest of wheat, Triticum aestivum, and barley, Hordeum vulgare, causes huge economic losses in Africa, South America, and North America. Most acceptable and ecologically beneficial aphid management strategies include selection and breeding of D. noxia-resistant varieties, and numerous D. noxia resistance genes have been identified in T. aestivum and H. vulgare. North American D. noxia biotype 1 is avirulent to T. aestivum varieties possessing Dn4 or Dn7 genes, while biotype 2 is virulent to Dn4 and avirulent to Dn7. The current investigation utilized next-generation RNAseq technology to reveal that biotype 2 over expresses proteins involved in calcium signaling, which activates phosphoinositide (PI) metabolism. Calcium signaling proteins comprised 36% of all transcripts identified in the two D. noxia biotypes. Depending on plant resistance gene-aphid biotype interaction, additional transcript groups included those involved in tissue growth; defense and stress response; zinc ion and related cofactor binding; and apoptosis. Activation of enzymes involved in PI metabolism by D. noxia biotype 2 aphids allows depletion of plant calcium that normally blocks aphid feeding sites in phloem sieve elements and enables successful, continuous feeding on plants resistant to avirulent biotype 1. Inhibition of the key enzyme phospholipase C significantly reduced biotype 2 salivation into phloem and phloem sap ingestion.

Despite the agricultural importance of species in the Grapholitini (Lepidoptera: Tortricidae), and the value of gene expression analysis for improved population management, few gene expression studies based on quantitative real-time PCR (qPCR) have been conducted for this tribe. Part of the reason for this lack of information is that suitable reference genes, which are fundamental for accurate normalization of qPCR studies, have not been identified for the tribe. Thus, the expression stability of six potential reference genes (ACT, AK, COI, EF1, ENO and TUB) was assessed in three different tissues (whole body, midgut and cuticle) of Cryptophlebia peltastica (Meyrick), Cydia pomonella (L.) and Thaumatotibia leucotreta (Meyrick). Additionally, these reference genes were tested using T. leucotreta at different temperatures (15°C, 25°C and 35°C) with and without baculovirus infection. Suitable reference genes were identified for the whole body and midgut tissue of all three species, and for cuticle tissue of Cy. pomonella and T. leucotreta. When T. leucotreta was infected with the virus at all temperature conditions ACT, AK and EF1 were found to be the most suitable reference genes for experimental normalization. In general, for all tissue types, species and stress conditions, AK and EF1 were the best-performing reference genes. However, even though the three species analysed were closely related and within the same tribe, each species required varying gene combinations for suitable normalization. This study provides the first reference gene evaluation for the Tortricidae, and paves the way for future qPCR analysis in Tortricidae.

FAH (fumarylacetoacetate hydrolase) catalyses the final step of tyrosine catabolism to produce fumarate and acetoacetate. HT1 (hereditary tyrosinaemia type 1) results from deficiency of this enzyme. Previously, we prepared a partial mimic of the putative tetrahedral intermediate in the reaction catalysed by FAH co-crystallized with the enzyme to reveal details of the mechanism [Bateman, Bhanumoorthy, Witte, McClard, Grompe and Timm (2001) J. Biol. Chem. 276, 15284–15291]. We have now successfully synthesized complete mimics CEHPOBA {4-[(2-carboxyethyl)-hydroxyphosphinyl]-3-oxobutyrate} and COPHPAA {3-[(3-carboxy-2-oxopropyl)hydroxyphosphinyl]acrylate}, which inhibit FAH in slow-onset tight-binding mode with Ki values of 41 and 12 nM respectively. A high-resolution (1.35 Å; 1 Å=0.1 nm) crystal structure of the FAH·CEHPOBA complex was solved to reveal the affinity determinants for these compounds and to provide further insight into the mechanism of FAH catalysis. These compounds are active in vivo, and CEHPOBA demonstrated a notable dose-dependent increase in SA (succinylacetone; a metabolite seen in patients with HT1) in mouse serum after repeated injections, and, following a single injection (1 μmol/g; intraperitoneal), only a modest regain of FAH enzyme activity was detected in liver protein isolates after 24 h. These potent inhibitors provide a means to chemically phenocopy the metabolic defects of either HT1 or FAH knockout mice and promise future pharmacological utility for hepatocyte transplantation. [ABSTRACT FROM AUTHOR]

The false codling moth, Thaumatotibia leucotreta (Meyrick), is a polyphagous pest indigenous to most of sub-Saharan Africa. This species is considered to be quarantined throughout much of the world, in part due to its extensive host range and significant damage caused by larval feeding. We developed a specific real-time PCR assay that allows for rapid and reliable identification of T. leucotreta. More than 150 target specimens were sequenced using an Illumina whole-genome shotgun approach to identify the most suitable loci for assay development. A hydrolysis probe that binds to a segment of the internal transcribed spacer 2 (ITS2) region was designed and used with a generic internal control targeting 18S rDNA. The assay was examined for cross-reactivity by testing additional Thaumatotibia species and representatives of related Olethreutine leafroller genera such as Cryptophlebia, Cydia, and Grapholita, which are often encountered in the same geographic region and on the same hosts as T. leucotreta. We compared our newly developed test to previously published TaqMan real-time PCR, SYBR Green real-time PCR, and loop-mediated isothermal amplification (LAMP) tests. Our newly developed real-time PCR assay outperformed all three tests in terms of analytical specificity, with 100% accuracy. These results will help to further improve diagnostic standards for molecular identification of T. leucotreta. [Figure: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Helicoverpa armigera is among the most problematic agricultural pests worldwide due to its polyphagy and ability to evolve pesticide resistance. Molecular detection methods for H. armigera have been developed to track its spread, as such methods allow for rapid and accurate differentiation from the native sibling species H. zea. Droplet digital PCR (ddPCR) is a preferred method for bulk screening due to its accuracy and tolerance to PCR inhibitors; however, real-time PCR is less expensive and more widely available in molecular labs. Improvements to DNA extraction yield, purity, and throughput are crucial for real-time PCR assay optimization. Bulk DNA extractions have recently been improved to where real-time PCR sensitivity can equal that of ddPCR, but these new methods require significant time and specialized equipment. In this study, we improve upon previously published bulk DNA extraction methods by reducing bench time and materials. Our results indicate that the addition of caffeine and RNase A improves DNA extraction, resulting in lower Cq values during real-time PCR while reducing the processing time and cost per specimen. Such improvements will enable the use of high throughput screening methods across multiple platforms to improve the probability of detection of H. armigera.

Abstract Species identification is necessary to prevent introductions of exotic plant pests through global trade. Many of these pests are understudied and lack publicly available DNA sequence data on which rapid molecular identification methods can be based. One such lineage is the genus Chrysodeixis, which includes three species of potential concern for United States trade initiatives: C. includens, C. chalcites, and C. eriosoma. Here we describe a method to generate robust 45S rDNA profiles using long read sequencing in order to clarify evolutionary relationships and develop a real-time PCR identification technique. Such an identification tool will be useful in rapidly differentiating between Chrysodeixis species of quarantine concern where traditional morphological identification methods are insufficient. Molecular methods such as this greatly reduce the time spent identifying each specimen, allow for detection of eDNA, vastly increase throughput, and increase the probability of detection. The methods presented here will be generally adaptable to any understudied lepidopteran taxa that necessitates a molecular diagnostic assay and, with adjustment or testing of the primers, could be applied to any group for which development of rDNA profiles in a benchtop setting would prove useful.

Seascape genomics provides a powerful framework to evaluate the presence and strength of environmental pressures on marine organisms, as well as to forecast long term species stability under various perturbations. In the highly productive North Pacific, forage fishes, key trophic links across ecosystems, are also contending with a rapidly warming climate and a litany of associated oceanographic changes (e.g., changes in salinity, dissolved oxygen, pH, primary production, etc.). These changes can place substantial selective pressures on populations over space and time. While several population genomics studies have targeted forage fishes in the North Pacific, none have formally analyzed the interactions between genotype and environment. However, when population genomics studies provide collection location information and other critical data, it is possible to supplement a published genomic dataset with environmental data from existing public databases and perform “post hoc seascape genomics” analyses. In reviewing the literature, we find pertinent metadata (dates and locations of sample collection) are rarely provided. We identify specific factors that may impede the application of seascape genomics methods in the North Pacific. Finally, we present an approach for supplementing data in a reproducible way to allow for post hoc seascape genomics analysis, in instances when metadata are reported. Overall, our goal is to demonstrate – via literature review – the utility and importance of seascape genomics to understanding the long term health of forage fish species in the North Pacific.

This study was aimed to investigate the significant wheat yield losses in northern and central Iraq. The cause of these losses was examining the presence of wheat curl mite Aceria tosichella and three viruses vectored by this species – Wheat streak mosaic virus (WSMV), High Plains wheat mosaic virus (HPWMoV), and Triticum mosaic virus (TriMV). Mite specimens were collected from Erbil, Mosul, and Baghdad over three years (2020-2022) and identified using morphological characterization and DNA sequencing of the ITS region. Virus presence was determined using Double Antibody Sandwich-Enzyme-Linked Immunosorbent Assay (DAS-ELISA). Mites were identified conclusively as A. tosichella, providing the first record of this species in Iraq. All three viruses were found to be present, with WSMV having the largest presence as it was detected in 99.56%, then HPWMoV (79.5%) of mite colonies. This is the first record of HPWMoV anywhere in Eurasia besides Ukraine and its widespread presence in Iraq in all three sampled provinces. TriMV was detected only in Erbil. To date this virus has been recorded only in North America and its limited presence in Iraq. The confirmed presence of A. tosichella and three vectored-viruses in Iraq are all new records and critical information for reducing wheat yield losses in this country.

Background and Objective: Mindfulness has emerged as key construct in mental health over past decades. While current mindfulness-based interventions (MBIs) are usually rooted in Asian contemplative traditions, mindfulness practices can equally be found in other knowledge systems, including integrative medicine systems such as anthroposophic medicine (AM). The Activity-Based Stress Release (ABSR) program incorporates the latter as part of an 8-week-long online intervention combining mindfulness exercises, behavioral self-observation, and mindful movement practices derived from this integrative medicine frame. The program could offer additional means for cultivating mindfulness, thereby addressing the necessity for diverse approaches in conjunction with individual differences, diverse clinical demands, or restricted capacities to perform certain mindfulness practices. Using an observational repeated-measures design, the current study aimed to assess a large-scale online implementation of this program in terms of its feasibility, assessing perceived stress and mindfulness., Method: Individuals who enrolled in any of the 37 ABSR program iterations carried out during 2023 and agreed to participate in the study completed online surveys including validated stress and mindfulness scales at the beginning, middle, end, and follow up of the intervention. Linear-mixed models were used for data analysis., Results: A total of 830 individuals took part in the study, of which 53.5% filled in at least 2 surveys. In line with our expectation, mindfulness scores increased significantly over the course of the intervention, while stress scores decreased significantly in this timeframe. We further found differential effects of self-practice frequency and duration on the outcomes., Conclusion: This study provides a first indication of stress reduction in conjunction with the online implementation of this novel MBI. The work further suggests that this AM-based intervention indeed targets mindfulness, as do other MBIs, and that it is adaptable to an online format. However, given the observational single-arm design, controlled studies will be necessary to confirm these results. Nonetheless, the study adds a novel contribution to existent MBIs, which is significant in view of the need for diverse approaches to meet the heterogeneity of individual predispositions and clinical requirements. It remains to established by forthcoming research for which groups of individuals or clinical features this approach could be especially beneficial or less suitable., Competing Interests: TH was employed by company Eurythmy4you. The remaining 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 Timm, Ko, Hundhammer, Berlowitz and Wolf.)

Introduction: Cancer is a debilitating disease with an often chronic course. One of the most taxing and prevalent sequelae in this context is cancer-related fatigue (CRF) resulting from the disease and/or associated treatments. Over the last years mindfulness-based interventions such as eurythmy therapy (ERYT), a mindful-movement therapy from anthroposophic medicine, have emerged as promising adjunct therapies in oncology. This prospective study investigated an online implementation of ERYT for CRF using a single arm repeated-measures design based on two consecutive studies., Method: Study 1 consisted of an initial assessment before, during, after, and at follow up of a 6-week online ERYT-based program in a mixed sample of N  = 165 adults with or without cancer diagnosis. Study 2 involved a similar design with an adapted 8-week online ERYT-based program in a sample of N  = 125 adults who had been diagnosed with cancer. Outcomes were assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue, Perceived Stress Scale, Mindful Attention Awareness Scale, and Insomnia Severity Index (for Study 1 all, for Study 2 only the former three). We additionally performed an exploratory analysis regarding practice frequency and duration. Data were analyzed using Linear Mixed-Effect Models per outcome; ANOVA was used for practice times., Results: For Study 1, mixed-effects model estimates showed no significant effect on fatigue, but pointed to significantly improved emotional and physical well-being, reduced stress, as well as increased mindfulness (mixed subjects). Functional and social well-being or sleep quality did not change significantly. Study 2 model estimates on the other hand showed significantly improved CRF in conjunction with the ERYT-based online intervention, as well as improved stress and mindfulness scores (cancer-diagnosed subjects)., Conclusion: Taken together, while our results should be interpreted with caution given the single-arm design and relatively high dropout, they suggest online ERYT may be associated with a reduction in fatigue for individuals diagnosed with cancer, an increase in mindfulness, and benefits for stress and certain well-being indicators. The online group format is advantageous in view of affordability and accessibility, the latter being particularly relevant for individuals who due to high symptom severity cannot leave their homes. Randomized-controlled studies will be needed to confirm these findings., Competing Interests: TH works as a therapist at the health provider Eurythmy4you but was not involved in the collection, handling, or analysis of data in this study, which was done independently by the scientific authors. The remaining 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 Timm, Ko, Hundhammer, Berlowitz and Wolf.)

Introduction: Seasonal allergic rhinitis (SAR) is a common health condition that is associated with an increased risk for bronchial asthma. Besides conventional medicine, treatments from traditional, complementary and integrative medicine are widely used by individuals with SAR. This review aims to systematically summarize evidence on the efficacy, effectiveness, and safety of European/Western phytotherapy (PT) and medications from anthroposophic medicine (AM) in individuals with SAR., Methods: Four electronic databases were screened for clinical studies published between January 1990 and March 2023. The results were qualitatively synthesized and the study quality was assessed., Results: In total, 14 studies were included, 11 from European/Western PT and three from AM. About half of the studies were rated as being of sufficient quality. The most frequently studied plant was Petasites hybridus (butterbur), showing beneficial effects on immunological parameters, subjective symptoms, and nasal airflow. Beneficial immunological and clinical effects were also shown for an herbal preparation combining Citrus limonis (lemon) and Cydonia oblonga (quince). The medications examined by studies of sufficient quality were judged to be safe., Conclusion: In summary, this systematic review highlights two herbal preparations, one from European/Western PT and one from AM, that appear to be promising options in the treatment of SAR., (© 2024 S. Karger AG, Basel.)

Background: The team timeout (TTO) is a safety checklist to be performed by the surgical team prior to incision. Exchange of critical information is, however, important not only before but also during an operation and members of surgical teams frequently feel insufficiently informed by the operating surgeon about the ongoing procedure. To improve the exchange of critical information during surgery, the StOP?-protocol was developed: At appropriate moments during the procedure, the leading surgeon briefly interrupts the operation and informs the team about the current Status (St) and next steps/objectives (O) of the operation, as well as possible Problems (P), and encourages questions of other team members (?). The StOP?-protocol draws attention to the team. Anticipating the occurrence of StOP?-protocols may support awareness of team processes and quality issues from the beginning and thus support other interventions such as the TTO; however, it also may signal an additional demand and contribute to a phenomenon akin to "checklist fatigue." We investigated if, and how, the introduction of the StOP?-protocol influenced TTO quality., Methods: This was a prospective intervention study employing a pre-post design. In the visceral surgical departments of two university hospitals and one urban hospital the quality of 356 timeouts (out of 371 included operation) was assessed by external observers before (154) and after (202) the introduction of the StOP?-briefing. Timeout quality was rated in terms of timeout completeness (number of checklist items mentioned) and timeout quality (engagement, pace, social atmosphere, noise)., Results: As compared to the baseline, after the implementation of the StOP?-protocol, observed timeouts had higher completeness ratings ( F  = 8.69, p  = 0.003) and were rated by observers as higher in engagement ( F  = 13.48, p  < 0.001), less rushed ( F  = 14.85, p  < 0.001), in a better social atmosphere ( F  = 5.83, p  < 0.016) and less noisy ( F  = 5.35, p  < 0.022)., Conclusion: Aspects of TTO are affected by the anticipation of StOP?-protocols. However, rather than harming the timeout goals by inducing "checklist fatigue," it increases completeness and quality of the team timeout., 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 Timm-Holzer, Tschan, Keller, Semmer, Zimmermann, Huber, Hübner, Candinas, Demartines, Weber and Beldi.)

Objective: The coronavirus disease 2019 (COVID-19) pandemic has resulted in shortages of personal protective equipment (PPE), underscoring the urgent need for simple, efficient, and inexpensive methods to decontaminate masks and respirators exposed to severe acute respiratory coronavirus virus 2 (SARS-CoV-2). We hypothesized that methylene blue (MB) photochemical treatment, which has various clinical applications, could decontaminate PPE contaminated with coronavirus., Design: The 2 arms of the study included (1) PPE inoculation with coronaviruses followed by MB with light (MBL) decontamination treatment and (2) PPE treatment with MBL for 5 cycles of decontamination to determine maintenance of PPE performance., Methods: MBL treatment was used to inactivate coronaviruses on 3 N95 filtering facepiece respirator (FFR) and 2 medical mask models. We inoculated FFR and medical mask materials with 3 coronaviruses, including SARS-CoV-2, and we treated them with 10 µM MB and exposed them to 50,000 lux of white light or 12,500 lux of red light for 30 minutes. In parallel, integrity was assessed after 5 cycles of decontamination using multiple US and international test methods, and the process was compared with the FDA-authorized vaporized hydrogen peroxide plus ozone (VHP+O 3 ) decontamination method., Results: Overall, MBL robustly and consistently inactivated all 3 coronaviruses with 99.8% to >99.9% virus inactivation across all FFRs and medical masks tested. FFR and medical mask integrity was maintained after 5 cycles of MBL treatment, whereas 1 FFR model failed after 5 cycles of VHP+O 3 ., Conclusions: MBL treatment decontaminated respirators and masks by inactivating 3 tested coronaviruses without compromising integrity through 5 cycles of decontamination. MBL decontamination is effective, is low cost, and does not require specialized equipment, making it applicable in low- to high-resource settings.

Background: Operations require collaboration between surgeons, anaesthetia professionals, and nurses. The aim of this study was to determine whether intraoperative briefings influence patient outcomes., Methods: In a before-and-after controlled trial (9 months baseline; 9 months intervention), intraoperative briefings were introduced in four general surgery centres between 2015 and 2018. During the operation, the responsible surgeon (most senior surgeon present) briefed the surgical team using the StOP? protocol about: progress of the operation (Status), next steps (Objectives), possible problems (Problems), and encouraged asking questions (?). Differences between baseline and intervention were analysed regarding surgical-site infections (primary outcome), mortality, unplanned reoperations, and duration of hospital stay (secondary outcomes), using inverse probability of treatment (IPT) weighting based on propensity scores., Results: In total, 8256 patients underwent surgery in the study. Endpoint data were available for 7745 patients (93.8 per cent). IPT-weighted and adjusted intention-to-treat analyses showed no differences in surgical-site infections between baseline and intervention (9.8 versus 9.6 per cent respectively; adjusted difference (AD) -0.15 (95 per cent c.i. -1.45 to 1.14) per cent; odds ratio (OR) 0.92, 95 per cent c.i. 0.83 to 1.15; P = 0.797), but there were reductions in mortality (1.6 versus 1.1 per cent; AD -0.54 (-1.04 to -0.03) per cent; OR 0.60, 0.39 to 0.92; P = 0.018), unplanned reoperations (6.4 versus 4.8 per cent; AD -1.66 (-2.69 to -0.62) per cent; OR 0.72, 0.59 to 0.89; P = 0.002), and fewer prolonged hospital stays (21.6 versus 19.8 per cent; AD -1.82 (-3.48 to -0.15) per cent; OR 0.87, 0.77 to 0.98; P = 0.024)., Conclusion: Short intraoperative briefings improve patient outcomes and should be performed routinely., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd.)

Selective pressures drive adaptive changes in the coronavirus spike proteins directing virus-cell entry. These changes are concentrated in the amino-terminal domains (NTDs) and the receptor-binding domains (RBDs) of complex modular spike protein trimers. The impact of this hypervariability on virus entry is often unclear, particularly with respect to sarbecovirus NTD variations. Therefore, we constructed indels and substitutions within hypervariable NTD regions and used severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus-like particles and quantitative virus-cell entry assays to elucidate spike structures controlling this initial infection stage. We identified NTD variations that increased SARS-CoV-2 spike protein-mediated membrane fusion and cell entry. Increased cell entry correlated with greater presentation of RBDs to ACE2 receptors. This revealed a significant allosteric effect, in that changes within the NTDs can orient RBDs for effective virus-cell binding. Yet, those NTD changes elevating receptor binding and membrane fusion also reduced interdomain associations, leaving spikes on virus-like particles susceptible to irreversible inactivation. These findings parallel those obtained decades ago, in which comparisons of murine coronavirus spike protein variants established inverse relationships between membrane fusion potential and virus stability. Considerable hypervariability in the SARS-CoV-2 spike protein NTDs also appear to be driven by counterbalancing pressures for effective virus-cell entry and durable extracellular virus infectivity. These forces may selectively amplify SARS-CoV-2 variants of concern. IMPORTANCE Adaptive changes that increase SARS-CoV-2 transmissibility may expand and prolong the coronavirus disease 2019 (COVID-19) pandemic. Transmission requires metastable and dynamic spike proteins that bind viruses to cells and catalyze virus-cell membrane fusion. Using newly developed assays reflecting these two essential steps in virus-cell entry, we focused on adaptive changes in SARS-CoV-2 spike proteins and found that deletions in amino-terminal domains reset spike protein metastability, rendering viruses less stable yet more poised to respond to cellular factors that prompt entry and subsequent infection. The results identify adjustable control features that balance extracellular virus stability with facile virus dynamics during cell entry. These equilibrating elements warrant attention when monitoring the evolution of pandemic coronaviruses.

Research on infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is currently restricted to BSL-3 laboratories. SARS-CoV2 virus-like particles (VLPs) offer a BSL-1, replication-incompetent system that can be used to evaluate virus assembly and virus-cell entry processes in tractable cell culture conditions. Here, we describe a SARS-CoV2 VLP system that utilizes nanoluciferase (Nluc) fragment complementation to track assembly and entry. We utilized the system in two ways. Firstly, we investigated the requirements for VLP assembly. VLPs were produced by concomitant synthesis of three viral membrane proteins, spike (S), envelope (E), and matrix (M), along with the cytoplasmic nucleocapsid (N). We discovered that VLP production and secretion were highly dependent on N proteins. N proteins from related betacoronaviruses variably substituted for the homologous SARS-CoV2 N, and chimeric betacoronavirus N proteins effectively supported VLP production if they contained SARS-CoV2 N carboxy-terminal domains (CTD). This established the CTDs as critical features of virus particle assembly. Secondly, we utilized the system by investigating virus-cell entry. VLPs were produced with Nluc peptide fragments appended to E, M, or N proteins, with each subsequently inoculated into target cells expressing complementary Nluc fragments. Complementation into functional Nluc was used to assess virus-cell entry. We discovered that each of the VLPs were effective at monitoring virus-cell entry, to various extents, in ways that depended on host cell susceptibility factors. Overall, we have developed and utilized a VLP system that has proven useful in identifying SARS-CoV2 assembly and entry features.

In mentally healthy individuals, autobiographical memory is typically biased toward positive events, which may help to maintain psychological well-being. Our aim was to assess a range of important positive memory biases in the mentally healthy and explore the possibility that these biases are mitigated in those with mental health problems. We administered a novel recall paradigm that required recollection of multiple good and bad past events (the Good Day-Bad Day task) to healthy and depressed individuals. This allowed us to explore differences in memory category fluency (i.e., the ability to generate integrated sets of associated events) for positive and negative memories, along with memory specificity, and fading affect bias-a greater reduction in the intensity of memory-related affect over time for negative versus positive events. We found that healthy participants demonstrated superior category fluency for positive relative to negative events but that this effect was absent in depressed participants. Healthy participants exhibited a strong fading affect bias that was significantly mitigated, although still present, in depression. Finally, memory specificity was reduced in depression for both positive and negative memories. Findings demonstrate that the positive bias associated with mental health is maintained by multiple autobiographical memory processes and that depression is as much a function of the absence of these positive biases as it is the presence of negative biases. Results provide important guidance for developing new treatments for improving mental health. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Background: Tense communication and disruptive behaviors during surgery have often been attributed to surgeons' personality or hierarchies, while situational triggers for tense communication were neglected. Goals of this study were to assess situational triggers of tense communication in the operating room and to assess its impact on collaboration quality within the surgical team., Methods and Findings: The prospective observational study was performed in two university hospitals in Europe. Trained external observers assessed communication in 137 elective abdominal operations led by 30 different main surgeons. Objective observations were related to perceived collaboration quality by all members of the surgical team. A total of 340 tense communication episodes were observed (= 0.57 per hour); mean tensions in surgeries with tensions was 1.21 per hour. Individual surgeons accounted for 24% of the variation in tensions, while situational aspects accounted for 76% of variation. A total of 72% of tensions were triggered by coordination problems; 21.2% by task-related problems and 9.1% by other issues. More tensions were related to lower perceived teamwork quality for all team members except main surgeons. Coordination-triggered tensions significantly lowered teamwork quality for second surgeons, scrub technicians and circulators., Conclusions: Although individual surgeons differ in their tense communication, situational aspects during the operation had a much more important influence on the occurrence of tensions, mostly triggered by coordination problems. Because tensions negatively impact team collaboration, surgical teams may profit from improving collaboration, for instance through training, or through reflexivity., Competing Interests: The authors have declared that no competing interests exist.

Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: The aim of this study was to evaluate the effectiveness of city Rest Break Ordinance (RBO) policies in expanding access to rest at work., Methods: We use data from surveys of construction workers in Austin and Dallas, Texas, in 2009, 2012, and 2015 (n = 557) to calculate the odds of receiving a rest break in pre- versus post-RBO Austin and in post-RBO Austin versus pre-RBO Dallas, controlling for demographic and employment characteristics., Results: Construction workers were 35% more likely to report receiving a rest break in Austin post-RBO and 16% less likely in Dallas without a RBO as compared to Austin with a RBO., Conclusion: The increased likelihood of receiving rest breaks at work in a RBO city suggests that, in the absence of enforceable national standards, city-level RBOs can be an important first step to effective prevention of heat-related illnesses (HRIs) and heat-related fatalities at work.

The use of intermittently administered doses of vasopressors to correct hypotension in the emergency department (ED), commonly referred to as bolus-dose pressors, push-dose pressors, Neo-sticks, or phenyl sticks, has been widely advocated outside of the traditional printed medical literature. No outcomes data of this practice exist to demonstrate benefits over traditional continuous infusion of vasopressors. Use of bolus-dose vasopressors in the ED setting raises a number of patient safety concerns, and misuse and errors in the preparation and administration of bolus-dose vasopressors may result in patient harm. A systems-based approach should be implemented to maximize safety and patient benefits if bolus-dose vasopressors are used. This article discusses the wide range of issues to consider when evaluating the role of bolus-dose vasopressors in the ED and provides recommendations based on current safe medication practices guidelines., (Copyright © 2017 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

A collaborative research study was conducted in order to improve our understanding of the source-to-receptor pathway for ambient fine particulate matter (aerodynamic diameter < or = 2.5 mu m; PM2.5) and subsequently to investigate the identity and sources of toxic components in PM2.5 responsible for adverse health effects in allergic humans. This research used a Harvard fine particle concentrator to expose Brown Norway rats, with and without ovalbumin-induced allergic airway disease, to concentrated air particles (CAPs) generated from ambient air in an urban Detroit community where the pediatric asthma rate was three times higher than the national average. Rats were exposed to CAPs during the exposure periods in July (mean = 676 microg/m3) and September (313 microg/m3) of 2000. Twenty-four hours after exposures lung lobes were either lavaged with saline to determine cellularity and protein in bronchoalveolar lavage fluid (BALF), or removed for analysis by inductively coupled plasma-mass spectrometry (ICP-MS) to detect ambient PM2.5-derived trace element retention. PM2.5 trace elements of anthropogenic origin, lanthanum (La), vanadium (V), manganese (Mn), and sulfur (S), were recovered from the lung tissues of CAPs-exposed rats. Recovery of those pulmonary anthropogenic particles was further increased in rats with allergic airways. In addition, eosinophils and protein in BALF were increased only in allergic animals exposed to CAPs. These results demonstrate preferential retention in allergic airways of air particulates derived from identified local combustion sources after a short-term exposure. Our findings suggest that the enhancement of allergic airway responses by exposure to PM2.5 is mediated in part by increased pulmonary deposition and localization of potentially toxic elements in urban air., (Copyright Taylor & Francis Inc.)

Epidemiological studies have reported that elevated levels of particulate air pollution in urban communities are associated with increases in attacks of asthma based on evidence from hospital admissions and emergency department visits. Principal pathologic features of chronic airway diseases, like asthma, are airway inflammation and mucous hypersecretion with excessive amounts of luminal mucus and increased numbers of mucus-secreting cells in regions of the respiratory tract that normally have few or no mucous cells (ie, mucous cell metaplasia). The overall goal of the present project was to understand the adverse effects of urban air fine particulate matter (PM2.5; < or = 2.5 pm in aerodynamic diameter)* on normal airways and airways compromised with airway inflammation and excess mucus. Our project was specifically designed to (1) examine the chemical and physical characteristics of PM2.5 and other airborne pollutants in the outdoor air of a local Detroit community with a high incidence of childhood asthma; (2) determine the effects of this community-based PM2.5 on the airway epithelium in normal rats and rats compromised with preexisting hypersecretory airway diseases (ie, animal models of human allergic airway disease--asthma and chronic bronchitis); and (3) identify the chemical or physical components of PM2.5 that are responsible for PM2.5 -induced airway inflammation and epithelial alterations in these animal models. Two animal models of airway disease were used to examine the effects of PM2.5 exposure on preexisting hypersecretory airways: neutrophilic airway inflammation induced by endotoxin challenge in F344 rats and eosinophilic airway inflammation induced by ovalbumin (OVA) challenge in BN rats. A mobile air monitoring and exposure laboratory equipped with inhalation exposure chambers for animal toxicology studies, air pollution monitors, and particulate collection devices was used in this investigation. The mobile laboratory was parked in a community in southwestern Detroit during the summer months when particulate air pollution is usually high (July and September 2000). We monitored the outdoor air pollution in this community daily, and exposed normal and compromised rats to concentrated PM2.5 from this local urban atmosphere. Rats in the inhalation studies were exposed for 1 day or for 4 or 5 consecutive days (10 hours/day) to either filtered air (controls) or concentrated ambient particles (CAPs) delivered by a Harvard ambient fine particle concentrator. Rats were killed 24 hours after the end of the exposure. Biochemical, morphometric, and molecular techniques were used to identify airway epithelial and inflammatory responses to CAPs. Lung lobes were also either intratracheally lavaged with saline to determine cellular composition and protein in bronchoalveolar lavage fluid (BALF) or removed for analysis by inductively coupled plasma-mass spectrometry (ICPMS) to detect retention of ambient PM2.5--derived trace elements. The Harvard concentrator effectively concentrated the fine ambient particles from this urban atmosphere (10-30 times) without significantly changing the major physicochemical features of the atmospheric particles. Daily CAPs mass concentrations during the 10-hour exposure period (0800-1800) in July ranged from 16 to 895 microg/m3 and in September ranged from 81 to 755 microg/m3. In general, chemical characteristics of ambient particles were conserved through the concentrator into the exposure chamber. Single or repeated exposures to CAPs did not cause adverse effects in the nasal or pulmonary airways of healthy F344 or BN rats. In addition, CAPs-related toxicity was not observed in F344 rats pretreated with bacterial endotoxin. Variable airway responses to CAPs exposure were observed in BN rats with preexisting allergic airway disease induced by OVA sensitization and challenge. Only OVA-challenged BN rats exposed to CAPs for 5 consecutive days in September 2000 had significant increases in airway mucosubstances and pulmonary inflammation compared to saline-challenged/air-exposed control rats. OVA-challenged BN rats that were repeatedly exposed to CAPs in July 2000 had only minor CAPs-related effects. In only the September 5-day exposure protocol, PM2.5 trace elements of anthropogenic origin (La, V, and S) were recovered from the lung tissues of CAPs-exposed rats. Recovery of these specific trace elements was greatest in rats with OVA-induced allergic airway disease. Additional laboratory experiments using intratracheal instillations of ambient PM2.5 samples were performed to identify bioactive agents in the CAPs to which rats had been exposed in the inhalation exposure component. Because the most pronounced effects of CAPs inhalation were found in BN rats with OVA-induced allergic airways exposed in September, we used ambient PM2.5 samples that were collected on 2 days during the September CAPs inhalation exposures to use for instillation. Ambient PM2.5 samples were collected, fractionated into soluble and insoluble species, and then compared with each other and with total PM2.5 for their effects in healthy BN rats and those with OVA-induced allergic airway disease. Intratracheal instillation of the insoluble fraction of PM2.5 caused mild neutrophilic inflammation in the lungs of healthy rats. However, total PM2.5 or the soluble or insoluble fractions instilled in rats with OVA-induced airway inflammation did not enhance the inflammation or the airway epithelial remodeling that was evident in some of the BN rats exposed to CAPs by inhalation. Therefore, the results from this instillation component did not suggest what fractions of the CAPs may have been responsible for enhancing OVA-induced airway mucosubstances and pulmonary inflammation observed in the inhalation exposure component. In summary, inhaled CAPs-related pulmonary alterations in the affected OVA-challenged rats appeared to be related to the chemical composition, rather than the mass concentration, to which the animals were exposed. Results of the trace element analysis in the lungs of CAPs-exposed BN rats exposed in September suggested that air particles derived from identified local combustion sources were preferentially retained in allergic airways. These results demonstrate that short-term exposures to CAPs from this southwestern Detroit community caused variable responses in laboratory rats and suggest that adverse biological responses to ambient PM2.5 may be associated more closely with local sources of particles and weather patterns than with particle mass.

At least three cultural circumstances have converged to make environmental health information critical, yet highly inaccessible, to many Americans: 1) the declining literacy levels of almost half the population, 2) the growing cultural diversity of the population, and 3) the complexity of environmental health information and science. This paper presents a case study of how literacy experts and environmental scientists partnered with a panel of inner-city residents to produce a community guide about brownfields, a process the authors refer to as "cooperative composing." The goal was to create low-barrier material (fifth-through-eight-grade reading level) that would inform people about brownfields issues so that they can meaningfully insert themselves into the process of planning for brownfields reuse and redevelopment. The authors structured an ongoing process with a panel of residents to learn with them just what types of information they wanted and what language level and graphics were appropriate. A primary motivator of this study was the belief that informed, activated residents will bring about greater equity and collaboration in environmental planning for brownfields.

We examined the incidence of health problems in elite-level amateur boxing athletes who sparred, trained, or competed at the United States Olympic Training Center in Colorado Springs, Colorado from January 1, 1977 through June 30, 1992. We think this is the first study to examine both injuries and illnesses in a population of elite-level athletes. We collected data on 1,776 reported problems (1219 injuries, 557 illnesses) from standard medical report forms completed by the permanent and volunteer sports medicine staff. We classified the information based on type, body region, location, description, and occurrence. There were significant differences between the frequency of injuries and illnesses and between the classifications and regions for each type of problem. Collectively, serious injuries represented only a relatively small percentage (6.1%) of all problems. We concluded that illnesses comprised a small but important portion of problems, that most illnesses involved respiratory tract infections (71%), that there is only a small risk for serious injury, and that injuries occur in a hierarchy of upper extremity (441, 25%), head/face (344, 19%), lower extremity (267, 15%), and spinal column (167, 9%) for amateur boxers.

In an experiment with growing Wistar rats of 100 g live weight the N-values and the 15N-frequency of the nitrogen in feces, urine and the experimental carcasses were determined after feeding 15N-labelled wheat. Proceeding from CZARNETZKI's multicompartment model (1969) for N-metabolism in monogastric animals, the measured data were used to calculate the endogenous and exogenous fecal N-proportion of total nitrogen. In agreement with earlier studies the intestinal nitrogen loss was found to rise as the protein intake increased. In this experiment, the intestinal nitrogen loss went up from 8.2 mg N/animal and day (N-free diet) to 33.9 mg N/animal and day at a daily nitrogen intake of 240 mg/animal and day. The true digestibility of the wheat protein (determined by taking into account the rise of fecal N loss) was 97.2% this value being 8.4 units higher than the true digestibility calculated by the conventional regressive method of fecal analysis with a constant value being taken for fecal N loss. In connection with earlier findings, this experiment allows to draw the conclusion that the true digestibility determined conventionally by regression analysis does not reflect the actual digestibility of the protein.