The TOXIN knowledge graph: supporting animal-free risk assessment of cosmetics.

The European Union's ban on animal testing for cosmetic products and their ingredients, combined with the lack of validated animal-free methods, poses challenges in evaluating their potential repeated-dose organ toxicity. To address this, innovative strategies like Next-Generation Risk Assessment (NGRA) are being explored, integrating historical animal data with new mechanistic insights from non-animal New Approach Methodologies (NAMs). This paper introduces the TOXIN knowledge graph (TOXIN KG), a tool designed to retrieve toxicological information on cosmetic ingredients, with a focus on liver-related data.

Exploring rural Scottish GPs' migration decisions: a secondary qualitative analysis considering burnout.

Background: The challenges of recruiting and retaining rural GPs are well described. UK data suggest high levels of burnout, characterised by detachment, exhaustion, and cynicism, plays a role in GP turnover. The contrast is engagement with work.

Toward a common interpretation of the 3Rs principles in animal research.

Many scientific breakthroughs have depended on animal research, yet the ethical concerns surrounding the use of animals in experimentation have long prompted discussions about humane treatment and responsible scientific practice. First articulated by Russell and Burch, the 3Rs Principles of Replacement, Reduction, and Refinement have gained widespread recognition as basic guidelines for animal research. Over time, the 3Rs have transcended the research community, influencing policy decisions, animal welfare advocacy and public perception of animal experimentation.

A robust high-throughput screening system to assess bacterial tyrosine ammonia lyase activity in the context of tyrosine inherited metabolic disorders.

Inborn errors of tyrosine metabolism result in patient's inability to degrade tyrosine. Current treatment consists of a phenylalanine and tyrosine restricted diet and nitisinone, causing a block in the tyrosine degradation pathway. However, tyrosine levels will increase, leading to acquired hypertyrosinemia, implying the need for an add-on treatment.

Improving quality in adult long covid services: Findings from the LOCOMOTION quality improvement collaborative.

The protracted form of COVID-19 known as 'long covid' was first described in 2020. Its symptoms, course and prognosis vary widely; some patients have a multi-system, disabling and prolonged illness. In 2021, ring-fenced funding was provided to establish 90 long covid clinics in England; some clinics were also established in Scotland and Wales.

The Immunological Profile of Adipose Mesenchymal Stromal/Stem Cells after Cell Expansion and Inflammatory Priming.

Background: AT-MSCs display great immunoregulatory features, making them potential candidates for cell-based therapy. This study aimed to evaluate the "RBC lysis buffer" isolation protocol and immunological profiling of the so-obtained AT-MSCs.

Methods: We established an immune-comparative screening of AT-MSCs throughout in vitro cell expansion (PM, P1, P2, P3, P4) and inflammatory priming regarding the expression of 28 cell-surface markers, 6 cytokines/chemokines, and 10 TLR patterns.

Efficacy and safety of faricimab for neovascular age-related macular degeneration: a systematic review and network meta-analysis.

Objective: To evaluate the efficacy and safety of faricimab compared with other anti-vascular endothelial growth factor (anti-VEGF) agents in treating neovascular age-related macular degeneration (nAMD) patients.

Methods And Analysis: A systematic review (SR) was conducted up to January 2023. Network meta-analyses (NMA) were performed, including sensitivity and subgroup analyses for naïve population.

Management of a large splenic hydatid cyst in pregnancy: A case report.

Splenic hydatid cysts are caused by the species and rarely occur in pregnancy. This case report describes the management of a 29-year-old pregnant woman with a large (11 × 8.7 × 10.

The short-term cost-effectiveness of once-weekly semaglutide versus once-weekly dulaglutide for the treatment of type 2 diabetes mellitus in Colombian adults.

Background: Type 2 Diabetes Mellitus (T2DM) is a highly prevalent disease worldwide and in Colombia, representing one of the main causes of death and placing a considerable burden on healthcare systems. 13 classes of drugs are approved for the treatment of T2DM, with Glucagon-like Peptide-1 (GLP-1) receptor agonists being a first-line treatment option for patients with or at high risk of certain cardiovascular diseases and chronic kidney disease. The objective of this study is to conduct a short-term cost-effectiveness analysis of once-weekly semaglutide versus once-weekly dulaglutide in Colombian adults with T2DM, from a third-party payer perspective.

Human skin stem cell-derived hepatic cells as in vitro drug discovery model for insulin-driven de novo lipogenesis.

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is characterized by intrahepatic triglyceride accumulation and can progress to metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis. Hepatic de novo lipogenesis (DNL), activated by glucose and insulin, is a central pathway contributing to early-stage development of MASLD. The emerging global prevalence of MASLD highlights the urgent need for pharmaceutical intervention to combat this health threat.

Will we ever be the same again? The mental health impact of the COVID-19 pandemic on health care staff and institutions.

As a group, health care workers (HCWs) were vulnerable to poor mental health (MH) prior to the COVID-19 pandemic. The added burdens of COVID-19 have put extra stressors on the health system and its most precious resource-its workers. This pandemic has exacerbated already poor MH in HCWs, leading to a workforce that is burnt out and struggling to cope with growing demands.

Hereditary Tyrosinemia Type 1 Mice under Continuous Nitisinone Treatment Display Remnants of an Uncorrected Liver Disease Phenotype.

Hereditary tyrosinemia type 1 (HT1) is a genetic disorder of the tyrosine degradation pathway (TIMD) with unmet therapeutic needs. HT1 patients are unable to fully break down the amino acid tyrosine due to a deficient fumarylacetoacetate hydrolase (FAH) enzyme and, therefore, accumulate toxic tyrosine intermediates. If left untreated, they experience hepatic failure with comorbidities involving the renal and neurological system and the development of hepatocellular carcinoma (HCC).

Flourishing During the COVID-19 Pandemic: A Longitudinal Study in South Africa.

In this longitudinal study, we examine changes in psychological distress and multidimensional well-being from before to during the COVID-19 pandemic among South African adults. As a secondary purpose, we explore whether pre-pandemic flourishing is protective against subsequent psychological distress during the public health crisis. The analytic sample ( = 293; = 44.

Clinical and therapeutic characterisation of a multicentre cohort of patients with inflammatory bowel disease in Colombia.

Introduction: In Latin America and Colombia there are few studies about the clinical and therapeutic characteristics of patients with inflammatory bowel disease (IBD). The objective of this study is to obtain an approximation to these data from a sample of patients from different reference centres in Colombia.

Patients And Methods: Cross-sectional study in adult and paediatric patients, with IBD, attended ambulatory in 6 institutions in different cities, between 2017 and 2020 information was collected on different dates, about demographic, clinical, and therapeutic aspects.

A retrospective review of post-intubation sedation and analgesia practices in a South African private ambulance service.

Introduction: Adequate post-intubation sedation and analgesia (PISA) practices are important in the pre-hospital setting where vibration and noise of the transport vehicle may contribute to anxiety and pain in the patient. These practices are poorly described in the pre-hospital setting. This study aims to describe the current pre-hospital PISA practices in a private South African (SA) emergency medical service.

A robust bacterial high-throughput screening system to evaluate single nucleotide polymorphisms of human homogentisate 1,2-dioxygenase in the context of alkaptonuria.

Alkaptonuria (AKU) is a rare inborn error of metabolism caused by a defective homogentisate 1,2-dioxygenase (HGD), an enzyme involved in the tyrosine degradation pathway. Loss of HGD function leads to the accumulation of homogentisic acid (HGA) in connective body tissues in a process called ochronosis, which results on the long term in an early-onset and severe osteoarthropathy. HGD's quaternary structure is known to be easily disrupted by missense mutations, which makes them an interesting target for novel treatment strategies that aim to rescue enzyme activity.

Mesenchymal Stem/Stromal Cells as a Therapeutic Tool in Cell-Based Therapy and Regenerative Medicine: An Introduction Expertise to the Topical Collection.

We are pleased to present this opening editorial, introducing our topical collection, "The New Era of Mesenchymal Stromal/Stem Cell Functional Application: State of the Art, Therapeutic Challenges and Future Directions" [...

Optical refrigeration of payloads to T < 125 K.

A modified all-solid-state optical cryocooler prototype based on anti-Stokes fluorescence in a 10%-doped Yb:YLF crystal cooled a payload to temperatures below 125 K starting from room temperature. To achieve this record performance, the optical refrigerator employed a novel, to the best of our knowledge, textured-MgF thermal link to improve the thermal transport and fluorescence escape. Additionally, it used spectrally selective, high-reflection coatings in the pump circulator cavity to suppress parasitic lasing and amplified spontaneous emission.

Development of an adverse outcome pathway network for breast cancer: a comprehensive representation of the pathogenesis, complexity and diversity of the disease.

Adverse outcome pathways (AOPs), introduced in modern toxicology, intend to provide an evidence-based representation of toxicological effects and facilitate safety assessment of chemicals not solely based on laboratory animal in vivo experiments. However, some toxicological processes are too complicated to represent in one AOP. Therefore, AOP networks are developed that help understanding and predicting toxicological processes where complex exposure scenarios interact and lead to the emergence of the adverse outcome.

The mental health of healthcare workers during the COVID-19 pandemic: a narrative review.

Purpose Of Review: Mental health (MH) problems among healthcare workers (HCWs) have the potential to impact negatively on the capacity of health systems to respond effectively to COVID-19. A thorough understanding of the factors that degrade or promote the MH of HCWs is needed to design and implement suitable intervention strategies to support the wellbeing of this population.

Recent Findings: MH problems among HCWs were elevated prior to the COVID-19 pandemic.

Light triggered nanoscale biolistics for efficient intracellular delivery of functional macromolecules in mammalian cells.

Biolistic intracellular delivery of functional macromolecules makes use of dense microparticles which are ballistically fired onto cells with a pressurized gun. While it has been used to transfect plant cells, its application to mammalian cells has met with limited success mainly due to high toxicity. Here we present a more refined nanotechnological approach to biolistic delivery with light-triggered self-assembled nanobombs (NBs) that consist of a photothermal core particle surrounded by smaller nanoprojectiles.