International Consensus Guidance for the Management of Glucocorticoid Related Complications in Neuromuscular Disease.

Introduction/aims: Glucocorticoid (GC)-related adverse reactions and risks are commonly seen during the treatment of immune-mediated and inflammatory neuromuscular disorders. There is wide variation in the management of associated complications. The aim of this study is to develop international consensus guidance on the management of GC-related complications in neuromuscular disorders.

Mesenchymal stem cell based therapies for uveitis: a systematic review of preclinical studies.

Cell therapy has shown promising results for treating uveitis in preclinical studies. As the field continues to grow towards clinical translation, it is important to review and critically appraise existing studies. Herein, we analysed and critically appraised all preclinical studies using cell therapy or cell derived extracellular vesicles (EVs) for uveitis, and provided insight into mechanisms regulating ocular inflammation.

Obesity-related T cell dysfunction impairs immunosurveillance and increases cancer risk.

Obesity is a well-established risk factor for human cancer, yet the underlying mechanisms remain elusive. Immune dysfunction is commonly associated with obesity but whether compromised immune surveillance contributes to cancer susceptibility in individuals with obesity is unclear. Here we use a mouse model of diet-induced obesity to investigate tumor-infiltrating CD8  T cell responses in lean, obese, and previously obese hosts that lost weight through either dietary restriction or treatment with semaglutide.

A far-ultraviolet-driven photoevaporation flow observed in a protoplanetary disk.

Most low-mass stars form in stellar clusters that also contain massive stars, which are sources of far-ultraviolet (FUV) radiation. Theoretical models predict that this FUV radiation produces photodissociation regions (PDRs) on the surfaces of protoplanetary disks around low-mass stars, which affects planet formation within the disks. We report James Webb Space Telescope and Atacama Large Millimeter Array observations of a FUV-irradiated protoplanetary disk in the Orion Nebula.

Efficacy of intravitreal dexamethasone implant used as monotherapy for the treatment of macular edema in non-infectious uveitis: a retrospective analysis.

Background: Uveitic macular edema is a complication of acute or chronic uveitis. Current treatment regiments frequently have numerous side effects, often requiring supplemental treatment. This study investigates the efficacy of dexamethasone (DEX) intravitreal implants as monotherapy for treatment of macular edema in non-infectious intermediate, posterior or panuveitis.

Dr. Gottlieb et al reply.

We thank the author for their reply and appreciate the approach of having clear terminology and standard definitions within clinical practice guidelines or recommendations, that are applicable across specialist groups. A definition of controlled anterior uveitis or quiescent disease is important for treatment decisions, particularly when classifying a patient's disease as failing current therapy and making decisions for escalating therapy.

gh-hroughput AMP ssay (HiTCA): A Novel Tool for Evaluating the Vitamin D-Dependent Antimicrobial Response.

Vitamin D is known to modulate human immune responses, and vitamin D deficiency is associated with increased susceptibility to infection. However, what constitutes sufficient levels or whether vitamin D is useful as an adjuvant therapeutic is debated, much in part because of inadequate elucidation of mechanisms underlying vitamin D's immune modulatory function. Cathelicidin antimicrobial peptide (CAMP) has potent broad-spectrum activity, and the gene is regulated in human innate immune cells by active 1,25(OH)D, a product of hydroxylation of inactive 25(OH)D by CYP27B1-hydroxylase.

Canadian Rheumatology Association Recommendations for the Screening, Monitoring, and Treatment of Juvenile Idiopathic Arthritis-Associated Uveitis.

Objective: To develop Canadian recommendations for the screening, monitoring, and treatment of uveitis associated with juvenile idiopathic arthritis (JIA).

Methods: Recommendations were developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-ADOLOPMENT approach. A working group of 14 pediatric rheumatologists, 6 ophthalmologists, 2 methodologists, and 3 caregiver/patient representatives reviewed recent American College of Rheumatology (ACR)/Arthritis Foundation (AF) recommendations and worked in pairs to develop evidence-to-decision (EtD) tables.

A novel 5-ring multifocal electroretinography stimulus for detecting hydroxychloroquine retinal toxicity.

Purpose: Multifocal electroretinogram (mfERG) shows great utility as a screening tool to detect early hydroxychloroquine (HCQ) retinopathy, but its widespread use is limited by the lack of accessibility and long test duration. In this study, we evaluated a novel concentric 5-ring mfERG stimulus to provide a simplified and rapid protocol for screening HCQ toxicity.

Methods: Patients referred for HCQ retinopathy screening were consented to this observational cross-sectional study.

Pathophysiology of central serous chorioretinopathy: a literature review with quality assessment.

The pathogenesis of central serous chorioretinopathy (CSCR), a pachychoroid disease, is poorly understood. While choroid hyperpermeability and retinal pigment epithelium dysfunction are cornerstones for developing CSCR, the mechanisms at the retinal, vascular, retinal pigment epithelium, and cellular level continue to be an enigma. A few preclinical studies and the development of small-sized, poorly controlled clinical trials have resulted in limited insight into the disease mechanism.

Intravenous administration of Penicillin results in therapeutic intravitreal levels in chronic postoperative endophthalmitis.

Importance: The role of systemic antibiotics in the treatment of bacterial endophthalmitis remains controversial. While penicillin is a highly effective antibiotic against bacteria that frequently cause endophthalmitis, the ability of systemically administered Penicillin G to penetrate into the vitreous at adequate therapeutic concentrations has not been studied. Its role in the treatment of endophthalmitis, particularly for bacteria for which it is the antibiotic of choice, therefore remains unknown.

(Sub)stellar companions shape the winds of evolved stars.

Binary interactions dominate the evolution of massive stars, but their role is less clear for low- and intermediate-mass stars. The evolution of a spherical wind from an asymptotic giant branch (AGB) star into a nonspherical planetary nebula (PN) could be due to binary interactions. We observed a sample of AGB stars with the Atacama Large Millimeter/submillimeter Array (ALMA) and found that their winds exhibit distinct nonspherical geometries with morphological similarities to planetary nebulae (PNe).

Uveitis and cystoid macular oedema secondary to topical prostaglandin analogue use in ocular hypertension and open angle glaucoma.

Background: Of the side effects of prostaglandin analogues (PGAs), uveitis and cystoid macular oedema (CME) have significant potential for vision loss based on postmarket reports. Caution has been advised due to concerns of macular oedema and uveitis. In this report, we researched and summarised the original data suggesting these effects and determined their incidence.

Ozurdex (dexamethasone intravitreal implant) for the treatment of intermediate, posterior, and panuveitis: a systematic review of the current evidence.

Background: This study aims to determine if the intravitreal dexamethasone implant (DEX implant, Ozurdex; Allergan, Inc., Irvine, California) is effective for treating intermediate, posterior, and panuveitis as a monotherapy or adjunctive treatment to systemic immunomodulatory therapies.

Methods: A systematic review using MEDLINE, EMBASE, and PubMed database searches was conducted with the Oxford Centre for Evidence-based Medicine Levels of Evidence criteria to select publications.

Vitamin D Binding Protein and the Biological Activity of Vitamin D.

Vitamin D has a long-established role in bone health. In the last two decades, there has been a dramatic resurgence in research interest in vitamin D due to studies that have shown its possible benefits for non-skeletal health. Underpinning the renewed interest in vitamin D was the identification of the vital role of intracrine or localized, tissue-specific, conversion of inactive pro-hormone 25-hydroxyvitamin D [25(OH)D] to active 1,25-dihydroxyvitamin D [1,25(OH)D].

A randomized, double-blind, window of opportunity trial evaluating the effects of chloroquine in breast cancer patients.

Purpose: Chloroquine has demonstrated anti-tumor activities through autophagy inhibition and cell cycle disruption. This study aimed to assess the effect of single-agent chloroquine on breast tumor cellular proliferation in a randomized, phase II, double-blind, placebo-controlled, pre-surgical window of opportunity trial.

Methods: Patients with newly diagnosed breast cancer were randomized 2:1 to chloroquine 500 mg daily or placebo for 2- to 6-weeks prior to their breast surgery.

Acute unfolding of a single protein immediately stimulates recruitment of ubiquitin protein ligase E3C (UBE3C) to 26S proteasomes.

The intracellular accumulation of aggregated misfolded proteins is a cytopathological hallmark of neurodegenerative diseases. However, the functional relationship between protein misfolding or aggregation and the cellular proteostasis network that monitors and maintains proteome health is poorly understood. Previous studies have associated translational suppression and transcriptional remodeling with the appearance of protein aggregates, but whether these responses are induced by aggregates or their misfolded monomeric or oligomeric precursors remains unclear.

The Diagnostic Utility of Multifocal Electroretinography in Detecting Chloroquine and Hydroxychloroquine Retinal Toxicity.

Purpose: To evaluate multifocal electroretinography (mfERG) as a screening test for detecting hydroxychloroquine and chloroquine toxicity.

Design: Diagnostic accuracy study.

Methods: Patients referred to the University of Ottawa for hydroxychloroquine or chloroquine retinopathy screening during 2011-2014 underwent 10-2 automated visual field, spectral domain optical coherence tomography, and mfERG testing.

Building Blocks of Dust: A Coordinated Laboratory and Astronomical Study of AGB Stars.

This article provides an overview of recent astronomical studies and a closely coordinated laboratory program devoted to the study of the physics and chemistry of carbon rich Asymptotic Giant Branch (AGB) stars. The increased sensitivity and angular resolution of high altitude ground-based millimeter-wave interferometers in the past few years has enabled molecular astronomers to determine the excitation and spatial distribution of molecules within a few stellar radii of the central star where the molecular seeds of dust are formed, and to critically assess the physicochemical mechanisms of dust formation and growth. However the astronomical studies are crucially dependent on precise laboratory measurements of the rotational spectra - both in the ground and vibrationally excited states of the normal and rare isotopic species - of the principal molecules in the inner region which appear to contain only two or three heavy atoms Much remains to be done by laboratory spectroscopists as evidenced by the large number of unassigned millimeters-wave rotational lines that are observed in the inner envelope of carbon rich AGB stars.

Intrinsic activation of the vitamin D antimicrobial pathway by M. leprae infection is inhibited by type I IFN.

Following infection, virulent mycobacteria persist and grow within the macrophage, suggesting that the intrinsic activation of an innate antimicrobial response is subverted by the intracellular pathogen. For Mycobacterium leprae, the intracellular bacterium that causes leprosy, the addition of exogenous innate or adaptive immune ligands to the infected monocytes/macrophages was required to detect a vitamin D-dependent antimicrobial activity. We investigated whether there is an intrinsic immune response to M.

Methotrexate for the treatment of noninfectious scleritis.

Objective: To assess corticosteroid-sparing and inflammation control in patients with noninfectious scleritis treated with methotrexate.

Design: Retrospective review.

Participants: Patients who received methotrexate treatment for noninfectious scleritis and who had 12 months of follow-up after treatment initiation were included in this review.