Tetraarylammonium salts - synthesis, properties and emerging use.

The chemistry of tetraarylammonium salts, first explored in the 1960s Soviet Union, has long been a dormant field of research. This is owing to the inherent difficulty in adding a fourth benzene ring to the nitrogen atom of the sterically demanding and low-nucleophilicity triphenylamine molecule. Only recently have new developments in synthetic methodology made access to tetraarylammonium salts less of a , and first applications are beginning to emerge.

'It's Got Its Ups and Downs': What People With Intellectual Disabilities Living in Supported Living and Residential Care Like and Dislike About Their Home.

Background: Given the current sociopolitical climate, people with intellectual disabilities are spending more time at home. Much housing-related research focuses on informant-completed measures and quantifiable outcomes. By contrast, this article explores the perspectives of adults with intellectual disabilities concerning what they liked or disliked about their homes.

Plug and play virus-like particles for the generation of anti-toxin antibodies.

Snakebite is a major global health concern, for which antivenom remains the only approved treatment to neutralise the harmful effects of the toxins. However, some medically important toxins are poorly immunogenic, resulting in reduced efficacy of the final product. Boosting the immunogenicity of these toxins in the commercial antivenom immunising mixtures could be an effective strategy to improve the final dose efficacy, and displaying snake antigens on Virus-like particles (VLPs) is one method for this.

Handheld Point-of-Care Devices for Snakebite Coagulopathy: A Scoping Review.

Venom-induced consumption coagulopathy (VICC) is a common complication of snakebite that is associated with hypofibrinogenemia, bleeding, disability, and death. In remote tropical settings, where most snakebites occur, the 20-minute whole blood clotting test is used to diagnose VICC. Point-of-care (POC) coagulation devices could provide an accessible means of detecting VICC that is better standardized, quantifiable, and more accurate.

Molecular dissection of cobra venom highlights heparinoids as an antidote for spitting cobra envenoming.

Snakebites affect about 1.8 million people annually. The current standard of care involves antibody-based antivenoms, which can be difficult to access and are generally not effective against local tissue injury, the primary cause of morbidity.

The Effects of Locus Coeruleus Optogenetic Stimulation on Global Spatiotemporal Patterns in Rats.

Whole-brain intrinsic activity as detected by resting-state fMRI can be summarized by three primary spatiotemporal patterns. These patterns have been shown to change with different brain states, especially arousal. The noradrenergic locus coeruleus (LC) is a key node in arousal circuits and has extensive projections throughout the brain, giving it neuromodulatory influence over the coordinated activity of structurally separated regions.

Improving assays in snake venom and antivenom research: A community discussion.

On the 26 January 2023, a free to attend, 'improving snake venom research: a community discussion' meeting was held virtually. This webinar brought together researchers from around the world to discuss current neutralisation of venom lethality mouse assays that are used globally to assess the efficacy of therapies for snakebite envenoming. The assay's strengths and weaknesses were highlighted, and we discussed what improvements could be made to refine and reduce animal testing, whilst supporting preclinical antivenom and drug discovery for snakebite envenoming.

African polyvalent antivenom can maintain pharmacological stability and ability to neutralise murine venom lethality for decades post-expiry: evidence for increasing antivenom shelf life to aid in alleviating chronic shortages.

Introduction: Antivenom is a lifesaving medicine for treating snakebite envenoming, yet there has been a crisis in antivenom supply for many decades. Despite this, substantial quantities of antivenom stocks expire before use. This study has investigated whether expired antivenoms retain preclinical quality and efficacy, with the rationale that they could be used in emergency situations when in-date antivenom is unavailable.

Assessing the spatial distribution of elemental concentrations in surface sediments of Lake Victoria, Kenya: implications for ecological health and management.

Lacustrine sediment quality indicates the effects of both natural and anthropogenic activities on the ecosystem and communities. Despite its ecological importance, myriad complexities, and potential contaminant sources, the spatial distribution of surficial sediments in Lake Victoria's Winam Gulf has never been comprehensively documented. The purpose of this study was to assess the spatial distribution, pathways, and ecological risk of metal elements in the lake using a sediment matrix.

Polymeric nanoparticle-based mRNA vaccine is protective against influenza virus infection in ferrets.

New therapies and vaccines based on nucleic acids combined with an efficient nanoparticle delivery vehicle have a broad applicability for different disease indications. An alternative delivery technology for the successfully applied lipid nanoparticles in mRNA SARS-CoV-2 vaccines are nanoparticles composed of biodegradable poly(amido)amine-based polymers with mRNA payload. To show that these polymeric nanoparticles can efficiently deliver influenza hemagglutinin mRNA to target tissues and elicit protective immune responses, a relevant ferret influenza challenge model was used.

Combinations of the azaquinazoline anti- agent, AWZ1066S, with benzimidazole anthelmintics synergise to mediate sub-seven-day sterilising and curative efficacies in experimental models of filariasis.

Lymphatic filariasis and onchocerciasis are two major neglected tropical diseases that are responsible for causing severe disability in 50 million people worldwide, whilst veterinary filariasis (heartworm) is a potentially lethal parasitic infection of companion animals. There is an urgent need for safe, short-course curative (macrofilaricidal) drugs to eliminate these debilitating parasite infections. We investigated combination treatments of the novel anti- azaquinazoline small molecule, AWZ1066S, with benzimidazole drugs (albendazole or oxfendazole) in up to four different rodent filariasis infection models: CB.

Nonuniform sliding-window reconstruction for accelerated dual contrast agent quantification with MR fingerprinting.

Objective: MR fingerprinting (MRF) can enable preclinical studies of cell tracking by quantifying multiple contrast agents simultaneously, but faster scan times are required for in vivo applications. Sliding window (SW)-MRF is one option for accelerating MRF, but standard implementations are not sufficient to preserve the accuracy of T*, which is critical for tracking iron-labelled cells in vivo.

Purpose: To develop a SW approach to MRF which preserves the T* accuracy required for accelerated concentration mapping of iron-labelled cells on single-channel preclinical systems.

Are Development Finance Institutions Meeting Their Human Rights Obligations in Health?

The right to the highest attainable standard of health is a fundamental right of every human being without distinction as to race, religion, political belief, or economic or social condition. Spent wisely, aid and other forms of government spending are essential for attaining this right, as well as driving development. However, taxpayer funds from high-income governments such as the UK, France, and Germany are increasingly being funneled through development finance institutions (DFIs) toward multi-million-dollar investments in for-profit health care corporations in low- and middle-income countries.

Dirofilariasis mouse models for heartworm preclinical research.

Introduction: Dirofilariasis, including heartworm disease, is a major emergent veterinary parasitic infection and a human zoonosis. Currently, experimental infections of cats and dogs are used in veterinary heartworm preclinical drug research.

Methods: As a refined alternative heartworm preventative drug screen, we assessed lymphopenic mouse strains with ablation of the interleukin-2/7 common gamma chain (γc) as susceptible to the larval development phase of .

Considerations for environmental biogeochemistry and food security for aquaculture around Lake Victoria, Kenya.

The impact of population expansion through economic growth and development has been identified as one of the key drivers of both water and sediment contamination from potentially harmful elements (PHEs). This presents a major hazard not only to aquatic ecosystems but local riparian communities and beyond who rely heavily on this natural resource for drinking water and fish-a valuable source of dietary micronutrients and protein. The present study measured biogeochemical concentration of PHEs in water, sediment and fish from locations pooled into four zones within Winam Gulf and Lake Victoria area of Kenya.

Infection with Seasonal H1N1 Influenza Results in Comparable Disease Kinetics and Host Immune Responses in Ferrets and Golden Syrian Hamsters.

Animal models of influenza are important in preclinical research for the study of influenza infection and the assessment of vaccines, drugs and therapeutics. Here, we show that Golden Syrian hamsters () inoculated via the intranasal route with high dose of influenza H1N1 display comparable disease kinetics and immune responses to the 'gold standard' ferret () model. We demonstrate that both the hamster and ferret models have measurable disease endpoints of weight loss, temperature change, viral shedding from the upper respiratory tract and increased lung pathology.

A new hazard assessment workflow to assess soil contamination from large and artisanal scale gold mining.

Gold mining activities are undertaken both at large and artisanal scale, often resulting in serious 'collateral' environmental issues, including environmental pollution and hazard to human and ecosystem health. Furthermore, some of these activities are poorly regulated, which can produce long-lasting damage to the environment and local livelihoods. The aim of this study was to identify a new workflow model to discriminate anthropogenic versus geogenic enrichment in soils of gold mining regions.

Age-dependent dysregulation of locus coeruleus firing in a transgenic rat model of Alzheimer's disease.

Hyperphosphorylated tau in the locus coeruleus (LC) is ubiquitous in prodromal Alzheimer's disease (AD), and LC neurons degenerate as AD progresses. Hyperphosphorylated tau alters firing rates in other brain regions, but its effects on LC neurons are unknown. We assessed single unit LC activity in anesthetized wild-type (WT) and TgF344-AD rats at 6 months, which represents a prodromal stage when LC neurons are the only cells containing hyperphosphorylated tau in TgF344-AD animals, and at 15 months when amyloid-β (Aβ) and tau pathology are both abundant in the forebrain.

Peri-Operative Risk Factors Associated with Post-Operative Cognitive Dysfunction (POCD): An Umbrella Review of Meta-Analyses of Observational Studies.

This umbrella review aimed to systematically identify the peri-operative risk factors associated with post-operative cognitive dysfunction (POCD) using meta-analyses of observational studies. To date, no review has synthesised nor assessed the strength of the available evidence examining risk factors for POCD. Database searches from journal inception to December 2022 consisted of systematic reviews with meta-analyses that included observational studies examining pre-, intra- and post-operative risk factors for POCD.

NKp46 natural killer cells develop an activated/memory-like phenotype and contribute to innate immunity against experimental filarial infection.

Lymphatic filariasis and onchocerciasis are major neglected tropical diseases affecting over 90 million people worldwide with painful and profoundly disfiguring pathologies (such as lymphoedema or blindness). Type 2 inflammation is a hallmark of filarial nematode tissue infection and is implicated both in eosinophil dependent immunity and lymphatic or ocular immunopathologies. Type-2 innate lymphoid cells (ILC2) are known to play an important role in the initiation of type 2 inflammation in helminth infection.

A mouse infection model and long-term lymphatic endothelium co-culture system to evaluate drugs against adult Brugia malayi.

The development of new drugs targeting adult-stage lymphatic filarial nematodes is hindered by the lack of a robust long-term in vitro culture model. Testing potential direct-acting and anti-Wolbachia therapeutic candidates against adult lymphatic filariae in vitro requires their propagation via chronic infection of gerbils. We evaluated Brugia malayi parasite burden data from male Mongolian gerbils compared with two immune-deficient mouse strains highly susceptible to B.

Intravenous tranexamic acid and thromboembolic events in hip fracture surgery: A systematic review and meta-analysis.

Background: Osteoporotic hip fractures are a major health problem in developed countries. Surgical management is the mainstay of treatment for these injuries, and historically presents an increased risk of thromboembolism, blood loss and blood transfusion. Despite the demonstrated safety of tranexamic acid (TXA) in elective hip arthroplasty, there is uncertainty regarding the risk of thromboembolism with the administration of TXA during hip fracture surgery.