Regulatory T cell expansion prevents retinal degeneration in type 2 diabetes.

Background: The global incidence of type 2 diabetes (T2D) is rapidly increasing, with retinopathy being its most common complication and a leading cause of preventable blindness. Although the precise mechanisms involved in the development of diabetic retinopathy (DR) are not fully understood, defective immunomodulation is a recognized key factor in its pathophysiology. Regulatory T cells (Treg) regulate inflammation and promote regeneration, and while they are known to have important anti-inflammatory and neuroprotective roles in other tissues, including central nervous system, their role in the diabetic retina remains largely unknown.

SARS-CoV-2 introductions to the island of Ireland: a phylogenetic and geospatiotemporal study of infection dynamics.

Background: Ireland's COVID-19 response combined extensive SARS-CoV-2 testing to estimate incidence, with whole genome sequencing (WGS) for genome surveillance. As an island with two political jurisdictions-Northern Ireland (NI) and Republic of Ireland (RoI)-and access to detailed passenger travel data, Ireland provides a unique setting to study virus introductions and evaluate public health measures. Using a substantial Irish genomic dataset alongside global data from GISAID, this study aimed to trace the introduction and spread of SARS-CoV-2 across the island.

Higher Intraocular Levels of Inflammatory Factors are Related to Retinal Vascular and Neurodegeneration in Myopic Retinopathy.

Purpose: In this study, we aimed to investigate the relationship between the intraocular levels of inflammatory factors and myopia-related retinal vascular and neuronal degeneration.

Patients And Methods: One hundred and forty-seven patients with Implantable Collamer Lens (ICL) implantation were enrolled and all participants received comprehensive ophthalmic examination. About 100~150 ul of aqueous humor was collected immediately before ICL surgery.

Promoting Prevention and Targeting Remission of Asthma A EUFOREA Consensus Statement on Raising the Bar in Asthma Care.

Topic Importance: Asthma is a common multifaceted respiratory disease with a major impact on quality of life. Despite increased insights into mechanisms underlying various asthma phenotypes/endotypes and the availability of targeted biologic treatment options, a substantial proportion of patients remains uncontrolled with risk of exacerbations, requiring systemic corticosteroids, and progressive disease. Current international guidelines advocate a personalized management approach to patients with uncontrolled severe asthma.

Protocol for single-molecule FISH in the developing mouse retinal vasculature.

The developing vasculature of the post-natal mouse retina is a powerful model to discover mechanisms of vessel formation and to test modulators of neovascularization. We present a protocol for single-molecule fluorescent in situ hybridization (smFISH) in whole-mount mouse retinas enabling the detection of individual mRNAs in vascular endothelial cells. We describe procedures from initial retina preparation to smFISH and detection.

It takes a village to raise a child- A multidisciplinary approach to promoting paediatric health literacy in cystic fibrosis.

Background: In Northern Ireland, approximately 550 people with cystic fibrosis (PwCF) attend the regional paediatric and adult centres within the Belfast Health and Social Care Trust. This autosomal recessive chronic condition necessitates regular clinical monitoring and a high treatment burden, as well as time implications for the maintenance of respiratory devices. Development of health literacy skills at an early age and promoting children with CF (CwCF) to take an active role in their healthcare has many advantages relating to their long-term self-care in preparation for transition from paediatric to adult care, decision-making and partnership engagement with the CF-multidisciplinary team (CF-MDT).

Biomarker-Guided Antibiotic Duration for Hospitalized Patients With Suspected Sepsis: The ADAPT-Sepsis Randomized Clinical Trial.

Importance: For hospitalized critically ill adults with suspected sepsis, procalcitonin (PCT) and C-reactive protein (CRP) monitoring protocols can guide the duration of antibiotic therapy, but the evidence of the effect and safety of these protocols remains uncertain.

Objective: To determine whether decisions based on assessment of CRP or PCT safely results in a reduction in the duration of antibiotic therapy.

Design, Setting, And Participants: A multicenter, intervention-concealed randomized clinical trial, involving 2760 adults (≥18 years), in 41 UK National Health Service (NHS) intensive care units, requiring critical care within 24 hours of initiating intravenous antibiotics for suspected sepsis and likely to continue antibiotics for at least 72 hours.

Animal-assisted intervention services across UK intensive care units: A national service evaluation.

Background: Animal-assisted interventions (AAI) can provide psychological support to critical care patients during their intensive care unit (ICU) admission. However, there are currently no data on AAI services across UK ICUs. The current study therefore aims to (i) determine how many ICUs in the UK offer services, (ii) characterise available services and (iii) explore and review local documentation for service oversight.

Airway total bacterial density, microbiota community composition and relationship with clinical parameters in bronchiectasis.

Background And Objective: This study explored the relationship between total bacterial density, airway microbiota composition and clinical parameters in bronchiectasis. We determined changes with time during clinical stability and following antibiotic treatment of a pulmonary exacerbation.

Methods: We conducted a multicentre longitudinal cohort study of UK participants with CT confirmed bronchiectasis.

Insights into the regulation of mRNA translation by scaffolding proteins.

Regionalisation of molecular mechanisms allows cells to fine-tune their responses to dynamic environments. In this context, scaffolds are well-known mediators of localised protein activity. These phenomenal proteins act as docking sites where pathway components are brought together to ensure efficient and reliable flow of information within the cell.

The effects of blood cell salvage on transfusion requirements after decannulation from veno-venous extracorporeal membrane oxygenation: an emulated trial analysis.

Background: Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is a supportive therapy for acute respiratory failure with increased risk of packed red blood cells (PRBC) transfusion. Blood cell salvage (BCS) aims to reduce blood transfusion, but its efficacy is unclear. This study aimed to estimate the effect of BCS at the time of removal of the ECMO circuit (ECMO decannulation) on PRBC transfused.

Improving health literacy and stakeholder-directed knowledge of One Health through analysis of readability: a cross sectional infodemiology study.

Background: The One Health approach involves collaboration across several sectors, including public health, veterinary and environmental sectors in an integrated manner. These sectors may be disparate and unrelated, however to succeed, all stakeholders need to understand what the other stakeholders are communicating. Likewise, it is important that there is public acceptance and support of One Health approaches, which requires effective communication between professional and institutional organisations and the public.

Sitagliptin eye drops prevent the impairment of retinal neurovascular unit in the new Trpv2 rat model.

Impaired function of the retinal neurovascular unit (NVU) is an early event in diabetic retinopathy (DR). It has been previously shown that topical delivery of the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin can protect against diabetes-mediated dysfunction of the retinal NVU in the db/db mouse. The aim of the present study was to examine whether sitagliptin could prevent the DR-like lesions within the NVU of the new non-diabetic model of DR, the Trpv2 knockout rat (Trpv2).

Intraocular complement activation is independent of systemic complement activation and is related to macular vascular remodelling in retinal vein occlusion.

Background: Retinal vein occlusion (RVO) is a major cause of vision loss. The pathogenesis remains poorly defined although inflammation is known to play a critical role. In this study, we investigated the levels of complement proteins in the aqueous humour and plasma of RVO participants and the relationship between complement levels and retinal pathologies.

Card9 and MyD88 differentially regulate Th17 immunity to the commensal yeast Malassezia in the murine skin.

The fungal community of the skin microbiome is dominated by a single genus, Malassezia. Besides its symbiotic lifestyle at the host interface, this commensal yeast has also been associated with diverse inflammatory skin diseases in humans and pet animals. Stable colonization is maintained by antifungal type 17 immunity.

Improved ion detection sensitivity in mass spectrometry imaging using tapping-mode scanning probe electrospray ionization to visualize localized lipids in mouse testes.

Mass spectrometry imaging (MSI) is a promising analytical method to visualize the distribution of lipids in biological tissues. To clarify the relationship between cellular distribution and lipid types in a tissue, it is crucial to achieve both an improvement in ion detection sensitivity and a reduction in the ionization area. We report methods for improving the efficiency of ion transfer to a mass spectrometer and miniaturizing the extraction area of a sample for tapping-mode scanning probe electrospray ionization (t-SPESI), atmospheric pressure sampling, and ionization methods.

Modified lipoprotein-induced sFlt1 production in human placental trophoblasts is mediated by protein kinase C.

Background: Preeclampsia is prevalent in women with diabetes, but the mechanism is unclear. We previously found that oxidized, glycated lipoproteins robustly upregulated soluble fms-like tyrosine kinase-1 (sFlt1), a key mediator of preeclampsia. Here, we determined the role of protein kinase C (PKC) and its subtypes in sFlt1 regulation in placental trophoblasts, and whether this mechanism might mediate the effect of modified lipoproteins.

Drug therapy versus placebo or usual care for comatose survivors of cardiac arrest; a systematic review with meta-analysis.

Background: In Europe, approximately 291,000 cardiac arrests occur annually. Despite critical care therapy, hospital mortality remains high. This systematic review assessed whether, in comatose survivors of cardiac arrest, any drug therapy, compared to placebo or usual care, improves outcomes.