Loss of NRF-2 and PGC-1α genes leads to retinal pigment epithelium damage resembling dry age-related macular degeneration.

Age-related macular degeneration (AMD) is a multi-factorial disease that is the leading cause of irreversible and severe vision loss in the developed countries. It has been suggested that the pathogenesis of dry AMD involves impaired protein degradation in retinal pigment epithelial cells (RPE). RPE cells are constantly exposed to oxidative stress that may lead to the accumulation of damaged cellular proteins, DNA and lipids and evoke tissue deterioration during the aging process.

The "Petechiae in children" (PiC) study: evaluating potential clinical decision rules for the management of feverish children with non-blanching rashes, including the role of point of care testing for Procalcitonin & Neisseria meningitidis DNA - a study protocol.

Background: Children commonly present to Emergency Departments (ED) with a non-blanching rash in the context of a feverish illness. While most have a self-limiting viral illness, this combination of features potentially represents invasive serious bacterial infection, including meningococcal septicaemia. A paucity of definitive diagnostic testing creates diagnostic uncertainty for clinicians; a safe approach mandates children without invasive disease are often admitted and treated with broad-spectrum antibiotics.

Antagonising Wnt/β-catenin signalling ameliorates lens-capsulotomy-induced retinal degeneration in a mouse model of diabetes.

Aims/hypothesis: Cataract surgery in diabetic individuals worsens pre-existing retinopathy and triggers the development of diabetic ocular complications, although the underlying cellular and molecular pathophysiology remains elusive. We hypothesise that lens surgery may exaggerate pre-existing retinal inflammation in diabetes, which may accelerate neurovascular degeneration in diabetic eyes.

Methods: Male heterozygous Ins2 mice (3 months of age) and C57BL/6 J age-matched siblings received either lens capsulotomy (to mimic human cataract surgery) or corneal incision (sham surgery) in the right eye.

A protocol for a systematic review of the diagnostic accuracy of Loop-mediated-isothermal AMPlification (LAMP) in diagnosis of invasive meningococcal disease in children.

Background: Meningococcal disease (MD) is notoriously difficult to diagnose in the early stages of the illness and presents similarly to many self-limiting viral infections. This mandates a cautious approach to diagnosis and initial management of suspected MD with many children receiving precautionary broad-spectrum intravenous antibiotics. Despite this approach, some children are still diagnosed late.

Mechanistical retinal drug targets and challenges.

The retina is constantly exposed to light that increases reactive oxygen species in retina. Oxidative stress, inflammation and neurodegeneration are the major contributors in the most common retinal diseases, such as age-related macular degeneration (AMD), glaucoma and diabetic retinopathy (DR). Emerging developments and research for novel therapy targets and drug delivery to the posterior segment offer a promising future for the treatment of retinal diseases including rare hereditary diseases.

Instrumental variable methods for a binary outcome were used to informatively address noncompliance in a randomized trial in surgery.

Objectives: Randomization can be used as an instrumental variable (IV) to account for unmeasured confounding when seeking to assess the impact of noncompliance with treatment allocation in a randomized trial. We present and compare different methods to calculate the treatment effect on a binary outcome as a rate ratio in a randomized surgical trial.

Study Design And Setting: The effectiveness of peeling versus not peeling the internal limiting membrane of the retina as part of the surgery for a full thickness macular hole.

A Low Concentration of Tacrolimus/Semifluorinated Alkane (SFA) Eyedrop Suppresses Intraocular Inflammation in Experimental Models of Uveitis.

Purpose: Corticosteroids remain the mainstay therapy for uveitis, a major cause of blindness in the working age population. However, a substantial number of patients cannot benefit from the therapy due to steroids resistance or intolerance. Tacrolimus has been used to treat refractory uveitis through systemic administration.

Antibiotic Capture by Bacterial Lipocalins Uncovers an Extracellular Mechanism of Intrinsic Antibiotic Resistance.

The potential for microbes to overcome antibiotics of different classes before they reach bacterial cells is largely unexplored. Here we show that a soluble bacterial lipocalin produced by upon exposure to sublethal antibiotic concentrations increases resistance to diverse antibiotics and These phenotypes were recapitulated by heterologous expression in of lipocalin genes from , , and methicillin-resistant Purified lipocalin bound different classes of bactericidal antibiotics and contributed to bacterial survival Experimental and X-ray crystal structure-guided computational studies revealed that lipocalins counteract antibiotic action by capturing antibiotics in the extracellular space. We also demonstrated that fat-soluble vitamins prevent antibiotic capture by binding bacterial lipocalin with higher affinity than antibiotics.

STAT3 Activation in Circulating Monocytes Contributes to Neovascular Age-Related Macular Degeneration.

Infiltrating macrophages are critically involved in pathogenic angiogenesis such as neovascular agerelated macular degeneration (nAMD). Macrophages originate from circulating monocytes and three subtypes of monocyte exist in humans: classical (CD14(+)CD16(-)), non-classical (CD14(-)CD16(+)) and intermediate (CD14(+)CD16(+)) monocytes. The aim of this study was to investigate the role of circulating monocyte in neovascular age-related macular degeneration (nAMD).