The percutaneous absorption of soman in a damaged skin porcine model and the evaluation of WoundStat™ as a topical decontaminant

PURPOSE: The aim of this study was to evaluate a candidate haemostat (WoundStat™), down-selected from previous in vitro studies, for efficacy as a potential skin decontaminant against the chemical warfare agent pinacoyl methylfluorophosphonate (Soman, GD) using an in vivo pig model. MATERIALS AND METHODS: An area of approximately 3 cm2 was dermatomed from the dorsal ear skin to a nominal depth of 100 µm. A discrete droplet of 14C-GD (300 µg kg-1) was applied directly onto the surface of the damaged skin at the centre of the dosing site. Animals assigned to the treatment group were given a 2 g application of WoundStat™ 30 s after GD challenge. The decontamination efficacy of WoundStat™ against GD was measured by the direct quantification of the distribution of 14C-GD, as well as routine determination of whole blood cholinesterase and physiological measurements. RESULTS: WoundStat™ sequestered approximately 70% of the applied 14C-GD. Internal radiolabel recovery from treated animals was approximately 1% of the initially applied dose. Whole blood cholinesterase levels decreased to less than 10% of the original value by 15 min post WoundStat™ treatment and gradually decreased until the onset of apnoea or until euthanasia. All treated animals showed signs of GD intoxication that could be grouped into early (mastication, fasciculations and tremor), intermediate (miosis, salivation and nasal secretions) and late onset (lacrimation, body spasm and apnoea) effects. Two of the six WoundStat™ treated animals survived the study duration. CONCLUSIONS: The current study has shown that the use of WoundStat™ as a decontaminant on damaged pig ear skin was unable to fully protect against GD toxicity. Importantly, the findings indicate that the use of WoundStat™ in GD contaminated wounds would not exacerbate GD toxicity. These data suggest that absorbent haemostatic products may offer some limited functionality as wound decontaminants.Peer reviewedFinal Accepted Versio

Efficient inference and identifiability analysis for differential equation models with random parameters

Heterogeneity is a dominant factor in the behaviour of many biological processes. Despite this, it is common for mathematical and statistical analyses to ignore biological heterogeneity as a source of variability in experimental data. Therefore, methods for exploring the identifiability of models that explicitly incorporate heterogeneity through variability in model parameters are relatively underdeveloped. We develop a new likelihood-based framework, based on moment matching, for inference and identifiability analysis of differential equation models that capture biological heterogeneity through parameters that vary according to probability distributions. As our novel method is based on an approximate likelihood function, it is highly flexible; we demonstrate identifiability analysis using both a frequentist approach based on profile likelihood, and a Bayesian approach based on Markov-chain Monte Carlo. Through three case studies, we demonstrate our method by providing a didactic guide to inference and identifiability analysis of hyperparameters that relate to the statistical moments of model parameters from independent observed data. Our approach has a computational cost comparable to analysis of models that neglect heterogeneity, a significant improvement over many existing alternatives. We demonstrate how analysis of random parameter models can aid better understanding of the sources of heterogeneity from biological data.Comment: Minor changes to text. Additional results in supplementary material. Additional statistics regarding results given in main and supplementary materia

Comparison of clinical and radiological outcomes for the anterior and medial approaches to open reduction in the treatment of bilateral developmental dysplasia of the hip:a systematic review protocol

Background: Developmental dysplasia of the hip (DDH) affects 1–3% of newborns and 20% of cases are bilateral. The optimal surgical management strategy for patients with bilateral DDH who fail bracing, closed reduction or present too late for these methods to be used is unclear. There are proponents of both medial approach open reduction (MAOR) and anterior approach open reduction (AOR); however, there is little evidence to inform this debate. Methods: We will perform a systematic review designed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol. We will search the medical and scientific databases including the grey and difficult to locate literature. The Medical Subject Headings “developmental dysplasia of the hip”, “congenital dysplasia of the hip”, “congenital hip dislocation”, “developmental hip dislocation”, and their abbreviations, “DDH” and “CDH” will be used, along with the qualifier “bilateral”. Reviewers will independently screen records for inclusion and then independently extract data on study design, population characteristics, details of operative intervention and outcomes from the selected records. Data will be synthesised and a meta-analysis performed if possible. If not possible we will analyse data according to Systematic Review without Meta-Analysis guidance. All studies will be assessed for risk of bias. For each outcome measure a summary of findings will be presented in a table with the overall quality of the recommendation assessed using the Grading of Recommendations Assessment Development and Evaluation approach. Discussion: The decision to perform MAOR or AOR in patients with bilateral DDH who have failed conservative management is not well informed by the current literature. High-quality, comparative studies are exceptionally challenging to perform for this patient population and likely to be extremely uncommon. A systematic review provides the best opportunity to deliver the highest possible quality of evidence for bilateral DDH surgical management. Systematic review registration: The protocol has been registered in the International Prospective Register of Systematic Reviews (PROSPERO ID CRD42022362325)

Influencia del uso de arena de cuarzo en el desgaste de adoquines que incorporan aluminato de estroncio

La presente investigación se llevó a cabo para diseñar adoquines bicapa fluorescentes con una resistencia a la compresión de 350 kgf/cm2. Estos adoquines incorporaron aluminato de estroncio (SrAl2O4:M), (M=Eu2+, Dy3+) y cuarzo (SiO2) en la mezcla, y se evaluó su influencia en el desgaste de la capa de rodadura. Para ello, se realizaron pruebas para determinar las propiedades físicas y mecánicas de los agregados, los cuales calificaron para ser utilizados en el diseño de la mezcla empleada en la fabricación de los adoquines. Una vez fabricado los adoquines, se llevaron a cabo pruebas de resistencia a la compresión y desgaste (método Böhme). Los resultados de compresión mostraron que, la combinación de aluminato de estroncio y cuarzo, no mejoraron la resistencia a la compresión, sin embargo, a los 14 días de curado la resistencia superaron sin dificultad los 350 kgf/cm2. En cuanto al desgaste, la influencia del SrAl2O4:M y SiO2, contribuyen a la disminución del desgaste en adoquines y el máximo valor que se registró fue de 11 765,13 mm3/5 000 mm2. Por otro lado, dosificar el SrAl2O4:M, respecto al peso del cemento no se obtuvieron resultados visibles de la intensidad de la luminiscencia, por tal motivo se fabricaron especímenes dosificados al peso de la mezcla del recibimiento.The present research was conducted to design fluorescent bilayer pavers with a compression strength of 350 kgf/cm2. These pavers incorporated strontium aluminate (SrAl2O4:M), (M=Eu2+, Dy3+) and quartz (SiO2) in the mix, and their influence on the wear of the wearing layer was evaluated. To achieve this, tests were carried out to determine the physical and mechanical properties of the aggregates, which qualified for use in the mix design employed in the manufacturing of the pavers. Once the pavers were manufactured, tests for compression strength and wear (Böhme method) were conducted. The compression results showed that the combination of strontium aluminate and quartz did not improve the compression strength; however, after 14 days of curing, the strength easily surpassed 350 kgf/cm2. Regarding wear, the influence of SrAl2O4:M and SiO2 contributed to the reduction of wear in the pavers, with the maximum recorded value being 11 765,13 mm3/ 5 000 mm2. On the other hand, dosing SrAl2O4:M, relative to the weight of the cement, did not yield visible results of the luminosity intensity; therefore, specimens were manufactured dosed based on the weight of the mix used

Finding the ‘Sweet Spot’ for reproductive performance in north Australian beef herds

We know that nutrition has a dominating effect on the reproductive performance of beef breeding females, but the level of pasture utilisation required for optimal cow herd production in northern Australia is unknown. We are using existing datasets to: 1) quantify the effect of pasture utilisation rates on reproductive performance (pregnancy, lactating cows pregnant within four months, calf loss and weaning percentage); 2) improve the capacity of existing models to predict cow performance and economics of herd management; and 3) recommend management to improve cow herd performance, production and profitability while maintaining the land and pasture resource for different land types and regions in northern Australia

The interaction of PRC2 with RNA or chromatin is mutually antagonistic

Polycomb repressive complex 2 (PRC2) modifies chromatin to maintain genes in a repressed state during development. PRC2 is primarily associated with CpG islands at repressed genes and also possesses RNA binding activity. However, the RNAs that bind PRC2 in cells, the subunits that mediate these interactions, and the role of RNA in PRC2 recruitment to chromatin all remain unclear. By performing iCLIP for PRC2 in comparison with other RNA binding proteins, we show here that PRC2 binds nascent RNA at essentially all active genes. Although interacting with RNA promiscuously, PRC2 binding is enriched at specific locations within RNAs, primarily exon-intron boundaries and the 3'UTR. Deletion of other PRC2 subunits reveals that SUZ12 is sufficient to establish this RNA binding profile. Contrary to prevailing models, we also demonstrate that the interaction of PRC2 with RNA or chromatin is mutually antagonistic in cells and in vitro. RNA degradation in cells triggers PRC2 recruitment to CpG islands at active genes. Correspondingly, release of PRC2 from chromatin in cells increases RNA binding. Consistent with this, RNA and nucleosomes compete for PRC2 binding in vitro. We propose that RNA prevents PRC2 recruitment to chromatin at active genes and that mutual antagonism between RNA and chromatin underlies the pattern of PRC2 chromatin association across the genome

Flupirtine as a Potential Treatment for Fibromyalgia

Fibromyalgia is a complex disorder characterised by chronic pain, fatigue, sleep disturbance and cognitive dysfunction with limited benefit gained with current therapies. The mean global prevalence of 2.7% is estimated for this chronic condition. Pharmacological and non-pharmacological therapeutic approaches are often required as treatments of the challenges associated with fibromyalgia. Flupirtine, a non-opioid drug, exhibits effective analgesia in a range of acute and persistent pain conditions, and evidence as treatment of fibromyalgia is considered. Activation of Kv7 potassium channels and agonism at gamma-aminobutyric acid receptor A leading to indirect N-methyl-D-aspartate receptor antagonism is responsible for the analgesic effects of flupirtine and appears to be involved in other symptoms associated with fibromyalgia. Patients with fibromyalgia reported improved control of their symptoms without significant adverse effects in an observational audit in clinical practice. This article presents evidence that flupirtine, or related drugs, is a therapeutic option for the treatment of fibromyalgia. The pharmacology of flupirtine and mechanisms of action involved provide a spectrum of effects that would not only control the chronic pain characteristic of fibromyalgia but many of the other symptoms. Thus, further investigation of the efficacy of flupirtine or related drugs exhibiting a similar pharmacology as a treatment of fibromyalgia would be of interest

Effectiveness of topical gabapentin in the treatment of vulvodynia: a narrative synthesis

Vulvodynia is a leading cause of dyspareunia in premenopausal women, causing considerable morbidity and sexual dysfunction. A multimodal approach is used to treat vulvodynia. Alongside psychosocial interventions and physiotherapy, pharmacological treatment such as oral gabapentin are used in the treatment of vulvodynia. Topical formulations of gabapentin have shown promise in animal models and case reports investigating its use in other pain conditions. The topical route also avoids the systemic complications of gabapentin such as somnolence, dizziness, and peripheral edema. This study aimed to perform a narrative synthesis of studies investigating the use of topical gabapentin in the treatment of vulvodynia. The primary outcome was a change in pain score following treatment with topical gabapentin. A broad literature search was performed, which identified four studies for inclusion. The included studies reported improved pain measures following treatment; however, conclusions cannot be made due to methodological heterogeneity and inherent limitations. These include lack of control arms, small sample sizes, lack of patient randomization, and use of combination treatments. Due to the paucity of evidence, this review supports the future implementation of double-blind randomized controlled trials to further investigate the efficacy of topical gabapentin in the treatment of vulvodynia

High-resolution temporal profiling of transcripts during Arabidopsis leaf senescence reveals a distinct chronology of processes and regulation

Leaf senescence is an essential developmental process that impacts dramatically on crop yields and involves altered regulation of thousands of genes and many metabolic and signaling pathways, resulting in major changes in the leaf. The regulation of senescence is complex, and although senescence regulatory genes have been characterized, there is little information on how these function in the global control of the process. We used microarray analysis to obtain a highresolution time-course profile of gene expression during development of a single leaf over a 3-week period to senescence. A complex experimental design approach and a combination of methods were used to extract high-quality replicated data and to identify differentially expressed genes. The multiple time points enable the use of highly informative clustering to reveal distinct time points at which signaling and metabolic pathways change. Analysis of motif enrichment, as well as comparison of transcription factor (TF) families showing altered expression over the time course, identify clear groups of TFs active at different stages of leaf development and senescence. These data enable connection of metabolic processes, signaling pathways, and specific TF activity, which will underpin the development of network models to elucidate the process of senescence

An Introduction To Marine Invasive Species

Countless marine species are invading new environments with devastating effects on the ecosystem, the local and global economy, and on human health. The frequency of marine invasions has been increasing in recent decades with a respective raised interest of invasive species in the scientific community, and the general public. The Aquatic Invasive Species class (MAR442) at the University of New England offers an informative overview of invasive species, targeting educated readers with a general interest in invasive species biology. Students in the MAR 442 class have worked on identifying the most important topics on marine invasive species, have reviewed the respective literature and written chapters that provide both a broad overview of the general aspects on marine invasions, as well as a set of individual case studies that illustrate different specific aspects of marine invasions. The class, comprised of fifteen junior and senior marine biology students, selected the different topics, presented the material, wrote the drafts, edited the drafts and assembled the final versions into this book. With a wealth of information on invasive species assembled in peer-reviewed articles, books, other literature, websites, data-bases and more, this book cannot claim to be all inclusive. However, we think that this book will provide an excellent broad overview of the most important aspects of marine invasion biology, and will furthermore provide very specific information on selected topics.https://dune.une.edu/marinesci_studproj/1000/thumbnail.jp