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Examining international practices in the management of pregnant women with von Willebrand disease
Background
The management of pregnant women with von Willebrand disease (VWD) is complex as physiological pregnancy-induced increases in plasma von Willebrand factor (VWF) may be blunted or absent. Women with VWD experience a heightened risk of postpartum hemorrhage (PPH) and special consideration must be given regarding neuraxial anesthesia (NA) and the need for prophylaxis at time of delivery. These challenges are compounded by a lack of robust evidence to guide clinical decision-making.
Objectives and Methods
To determine the current international clinical practices in the management of pregnancy for women with VWD, the International Society on Thrombosis and Haemostasis (ISTH) conducted an international survey of health-care providers (HCP).
Results
One hundred thirty-two respondents from 39 countries were included in the final analysis. Variations in clinical practice were identified in antenatal (monitoring of plasma VWF and ferritin levels), peripartum (optimal plasma VWF target at delivery) and postpartum management (definitions used for PPH and postpartum monitoring). A key area of divergence was suitability for NA for women with type 2 and type 3 VWD, with many respondents advising against the use of NA even with VWF supplementation (29% type 2 VWD, 37% type 3 VWD) but others advising use once plasma VWF activity was >50 IU/dL (57% type 2 VWD; 50% type 3 VWD).
Conclusions
This survey highlighted areas of uncertainty surrounding common management issues for pregnant women with VWD. These data underscore the need for international collaborative research efforts focused on peripartum management to improve care for pregnant women with VWD
Effect of dendron structure on the luminescent and charge transporting properties of solution processed dendrimer-based OLEDs
The photophysical and charge transport properties of neat and blend films of fac-tris[2-phenylpyridinato-C2,N]iridium(III) [Ir(ppy)3]-cored light-emitting dendrimers and tris(4-carbazoyl-9-ylphenyl)amine (TCTA)-based hosts, with each combination having the same first generation dendrons were measured and compared. The first generation dendrons were composed of bis(fluorenyl)carbazolyl with n-propyl surface groups, or biphenyl with 2-ethylhexyloxy or t-butyl surface groups. Dendronisation of the emitter and host was found to decrease the energy transfer efficiency from the host to the guest relative to an evaporated Ir(ppy)3:TCTA blend film, with the blend composed of materials with biphenyl dendrons and t-butyl surface groups having the largest decrease. The hole mobilities of the solution processed neat and blend layers were found to be 1–2 orders of magnitude lower than those of the equivalent evaporated films. The blend film containing the host and dendrimer with first generation biphenyl dendrons and 2-ethylhexyloxy surface groups had the highest photoluminescence quantum yield (PLQY), comparable to evaporated Ir(ppy)3:TCTA-based films but the lowest hole mobility (≈10−8 cm2 V−1 s−1). In contrast, the blend with the dendrimers composed of the bis(fluorenyl)carbazolyl dendrons with n-propyl surface groups had a low PLQY but higher hole mobility. It was found for the combinations of these solution processable materials that the hole mobility of the blend film was the limiting factor in OLED performance. Devices containing an emissive layer of the materials with the bis(fluorenyl)carbazolyl dendrons with n-propyl surface groups (11 mole percent of the emitter) had a PLQY of 40.8% but the highest external quantum efficiency of 10.0 ± 0.4%, reaching a maximum luminance of almost 10 000 cd m−2
Cat management in an unregulated shelter environment: Relationship between care provision and cat health in Hong Kong
Cat (Felis silvestris catus) shelter practices may have important implications for cats' health and well-being. This study explored the relationship between husbandry practices and cat health in Hong Kong's shelters which are unregulated. Cat health was measured via body condition score (BCS), coat condition and signs of oculo-nasal discharge. A total of 314 cats in 24 cat shelters were assessed. A satisfactory BCS was associated with regular veterinary input, more than once per day disinfection and more than once per day change of water. The presence of oculo-nasal discharge — as a marker for upper respiratory tract infection — was associated with a lack of regular veterinary input and less frequent change of water within the shelter. A lack of regular feeding was the only factor associated with a dull coat. In summary, this study showed that certain husbandry practices had important associations with different aspects of cats' health for cats housed in an unregulated shelter environment in Hong Kong. These findings provide evidence-based support for husbandry guidelines or regulations for cat shelters which could have a positive impact on shelter cats' health and welfare
Inoculation of barley with Trichoderma harzianum T-22 modifies lipids and metabolites to improve salt tolerance
Soil salinity has a serious impact on plant growth and agricultural yield. Inoculation of crop plants with fungal endophytes is a cost-effective way to improve salt tolerance. We used metabolomics to study how Trichoderma harzianum T-22 alleviates NaCl-induced stress in two barley (Hordeum vulgare L.) cultivars, Gairdner and Vlamingh, with contrasting salinity tolerance. GC-MS was used to analyse polar metabolites and LC-MS to analyse lipids in roots during the early stages of interaction with Trichoderma. Inoculation reversed the severe effects of salt on root length in sensitive cv. Gairdner and, to a lesser extent, improved root growth in more tolerance cv. Vlamingh. Biochemical changes showed a similar pattern in inoculated roots after salt treatment. Sugars increased in both cultivars, with ribulose, ribose, and rhamnose specifically increased by inoculation. Salt stress caused large changes in lipids in roots but inoculation with fungus greatly reduced the extent of these changes. Many of the metabolic changes in inoculated cv. Gairdner after salt treatment mirror the response of uninoculated cv. Vlamingh, but there are some metabolites that changed in both cultivars only after fungal inoculation. Further study is required to determine how these metabolic changes are induced by fungal inoculation
Anatomical evaluation of rat and mouse simulators for laboratory animal science courses
According to the European Directive 63/2010/EU, education and training involving living rats and mice are classified as an animal experiment and demands the implementation of the 3Rs. Therefore, as a method of refinement, rat and mouse simulators were developed to serve as an initial training device for various techniques, prior to working on living animals. Nevertheless, little is known about the implementation, anatomical correctness, learning efficiency and practical suitability of these simulators. With this in mind, a collaborative research project called “SimulRATor” was initiated to systematically evaluate the existing rat and mouse simulators in a multi-perspective approach. The objective of the study presented here was to identify the anatomical strengths and weaknesses of the available rat and mouse simulators and to determine anatomical requirements for a new anatomically correct rat simulator, specifically adapted to the needs of Laboratory Animal Science (LAS) training courses. Consequently, experts of Veterinary Anatomy and LAS evaluated the anatomy of all currently available rat and mouse simulators. The evaluation showed that compared to the anatomy of living rats and mice, the tails were perceived as the most anatomically realistic body part, followed by the general exterior and the limbs. The heads were rated as the least favored body part
Blister fluid as a cellular input for ex vivo diagnostics in drug-induced severe cutaneous adverse reactions improves sensitivity and explores immunopathogenesis
Background
Drug-induced severe cutaneous adverse reactions (SCARs) are presumed T-cell-mediated hypersensitivities associated with significant morbidity and mortality. Traditional in vivo testing methods, such as patch or intradermal testing, are limited by a lack of standardisation and poor sensitivity. Modern approaches to testing include measurement of IFN-γ release from patient peripheral blood mononuclear cells (PBMC) stimulated with the suspected causative drug.
Objective
We sought to improve ex vivo diagnostics for drug-induced SCAR by comparing enzyme-linked immunospot (ELISpot) sensitivities and flow cytometry-based intracellular cytokine staining (ICS) and cellular composition of separate samples (PBMC or blister fluid cells (BFC)) from the same donor.
Methods
IFN-γ release ELISpot and flow cytometry analyses were performed on donor-matched PBMC and BFC samples from four SCAR patients with distinct drug-hypersensitivity.
Results
Immune responses to suspected drugs were detected in both PBMC and BFC samples of two donors (Case 1 in response to ceftriaxone and Case 4 to oxypurinol), with BFC eliciting stronger responses. For two other donors, only BFC samples showed a response to meloxicam (Case 2) or sulfamethoxazole and its 4-nitro metabolite (Case 3). Consistently, flow cytometry revealed a greater proportion of IFN-γ-secreting cells in the BFC compared to PBMC. BFC cells from Case 3 were also enriched for memory/activation/tissue-recruitment markers over PBMC.
Conclusion
Analysis of BFC samples for drug-hypersensitivity diagnostics offers a higher sensitivity for detecting positive responses compared to PBMC. This is consistent with recruitment (and enrichment) of cytokine-secreting cells with a memory/activated phenotype into blisters
Speculative social science fiction of digitalization in higher education: From what is to what could be
[No abstract available
Identification of clandestine grave site by understanding location choices from an environmental and psychological perspective
What factors influence an offender’s decision-making process in choosing a particular clandestine grave site? This study attempts to answer this question and in doing so proposes that it is best answered using a multifaceted approach. This approach is required to appreciate how Winthropping is a relevant method to employ to understand these decisionmaking factors. An offender’s decision-making process is affected by theoretical underpinnings in forensic psychology and environmental criminology. Forensic psychology informs us that the environment plays a significant role in influencing decisions made by an offender, who scours it consciously and subconsciously for relevant information about how best to commit their crime. Environmental criminology states that these decisions aggregate to form larger trends about how crime is committed across geographical areas and how best we can use these to apprehend offenders. Furthermore, knowledge gained by applying statistical methods such as Matrix Forecasting, and Behavioural Sequence Analysis can form the foundation of testing whether Winthropping can be used as a clandestine grave search tool. Finally, the forensic components and unique characteristics of clandestine graves will be discussed in relation to Winthropping. The potential impact of this research may reduce the reliance on offenders telling us where to find their victims as well as provide a new method for investigators to use in their current cases
‘A flying start’: Wildlife trypanosomes in tissues of Australian tabanids (Diptera: Tabanidae)
Tabanids (syn. horse flies) are biting-flies of medical and veterinary significance because of their ability to transmit a range of pathogens including trypanosomes – some species of which carry a combined health and biosecurity risk. Invertebrate vectors responsible for transmitting species of Trypanosoma between Australian wildlife remains unknown, thus establishing the role of potential vector candidates such as tabanids is of utmost importance. The current study aimed to investigate the presence of indigenous trypanosomes in tabanids from an endemic area of south-west Australia. A total of 148 tabanids were collected, with morphological analysis revealing two subgenera: Scaptia (Pseudoscione) and S. (Scaptia) among collected flies. A parasitological survey using an HRM-qPCR and sequencing approach revealed a high (105/148; 71%) prevalence of trypanosomatid DNA within collected tabanids. Individual tissues - proboscis (labrum, labium and mandibles, hypopharynx), salivary glands, proventriculus, midgut, and hindgut and rectum - were also tested from a subset of 20 tabanids (n = 140 tissues), confirming the presence of Trypanosoma noyesi in 31% of screened tissues, accompanied by T. copemani (3%) and T. vegrandis/T.gilletti (5%). An unconfirmed trypanosomatid sp. was also detected (9%) within tissues. The difference between tissues infected with T. noyesi compared with tissues infected with other trypanosome species was statistically significant (p < 0.05), revealing T. noyesi as the more frequent species detected in the tabanids examined. Fluorescence in situ hybridisation (FISH) and scanning electron microscopy (SEM) confirmed intact parasites within salivary glands and the proboscis respectively, suggesting that both biological and mechanical modes of transmission could occur. This study reveals the presence of Australian Trypanosoma across tabanid tissues and confirms intact parasites within tabanid salivary glands and the proboscis for the first time. Further investigations are required to determine whether tabanids have the vectorial competence to transmit Australian trypanosomes between wildlife
Identification of metabolically quiescent Leishmania mexicana parasites in peripheral and cured dermal granulomas using stable isotope tracing imaging mass spectrometry
Leishmania are sandfly-transmitted protists that induce granulomatous lesions in their mammalian host. Although infected host cells in these tissues can exist in different activation states, the extent to which intracellular parasites stages also exist in different growth or physiological states remains poorly defined. Here, we have mapped the spatial distribution of metabolically quiescent and active subpopulations of Leishmania mexicana in dermal granulomas in susceptible BALB/c mice, using in vivo heavy water labeling and ultra high-resolution imaging mass spectrometry. Quantitation of the rate of turnover of parasite and host-specific lipids at high spatial resolution, suggested that the granuloma core comprised mixed populations of metabolically active and quiescent parasites. Unexpectedly, a significant population of metabolically quiescent parasites was also identified in the surrounding collagen-rich, dermal mesothelium. Mesothelium-like tissues harboring quiescent parasites progressively replaced macrophage-rich granuloma tissues following treatment with the first-line drug, miltefosine. In contrast to the granulomatous tissue, neither the mesothelium nor newly deposited tissue sequestered miltefosine. These studies suggest that the presence of quiescent parasites in acute granulomatous tissues, together with the lack of miltefosine accumulation in cured lesion tissue, may contribute to drug failure and nonsterile cure.
IMPORTANCE Many microbial pathogens switch between different growth and physiological states in vivo in order to adapt to local nutrient levels and host microbicidal responses. Heterogeneity in microbial growth and metabolism may also contribute to nongenetic mechanisms of drug resistance and drug failure. In this study, we have developed a new approach for measuring spatial heterogeneity in microbial metabolism in vivo using a combination of heavy water (2H2O) labeling and imaging mass spectrometry. Using this approach, we show that lesions contain a patchwork of metabolically distinct parasite populations, while the underlying dermal tissues contain a large population of metabolically quiescent parasites. Quiescent parasites also dominate drug-depleted tissues in healed animals, providing an explanation for failure of some first line drugs to completely eradicate parasites. This approach is broadly applicable to study the metabolic and growth dynamics in other host-pathogen interactions