OME-NGFF: a next-generation file format for expanding bioimaging data-access strategies.

The rapid pace of innovation in biological imaging and the diversity of its applications have prevented the establishment of a community-agreed standardized data format. We propose that complementing established open formats such as OME-TIFF and HDF5 with a next-generation file format such as Zarr will satisfy the majority of use cases in bioimaging. Critically, a common metadata format used in all these vessels can deliver truly findable, accessible, interoperable and reusable bioimaging data.

Senescent human melanocytes drive skin ageing via paracrine telomere dysfunction.

Cellular senescence has been shown to contribute to skin ageing. However, the role of melanocytes in the process is understudied. Our data show that melanocytes are the only epidermal cell type to express the senescence marker p16INK4A during human skin ageing. Aged melanocytes also display additional markers of senescence such as reduced HMGB1 and dysfunctional telomeres, without detectable telomere shortening. Additionally, senescent melanocyte SASP induces telomere dysfunction in paracrine manner and limits proliferation of surrounding cells via activation of CXCR3-dependent mitochondrial ROS. Finally, senescent melanocytes impair basal keratinocyte proliferation and contribute to epidermal atrophy in vitro using 3D human epidermal equivalents. Crucially, clearance of senescent melanocytes using the senolytic drug ABT737 or treatment with mitochondria-targeted antioxidant MitoQ suppressed this effect. In conclusion, our study provides proof-of-concept evidence that senescent melanocytes affect keratinocyte function and act as drivers of human skin ageing.

Misaligned foveal morphology and sector retinal dysfunction in AKT1-mosaic Proteus syndrome.

PURPOSE: Proteus syndrome arises as a result of a post-zygotic mosaic activating mutation in the AKT1 oncogene, causing a disproportionate overgrowth of affected tissues. A small number of ocular complications have been reported. We present the unique findings in a patient who had molecular confirmation of AKT1 mosaicism alongside fulfilling the clinical criteria for Proteus syndrome. METHODS: Pattern electroretinography, visual evoked potentials and multifocal electroretinography testing were performed alongside detailed retinal imaging and clinical examination to detail the ophthalmic characteristics. RESULTS: Electrophysiological findings characterised unilateral macular dysfunction alongside sector retinal dysfunction of the right eye. This was demonstrated through optical coherence tomography and ultra-wide-field imaging to be associated with a misaligned foveal morphology and sector retinal dysfunction extending into the temporal retina. CONCLUSION: We propose this patient has asymmetric foveal development and concomitant sector retinal dysfunction as the result of the mosaic AKT1 mutation, either through disruption in the retinal PI3K-AKT1 signalling pathway or through mechanical distortion of ocular growth, resulting in disproportionate inner retinal development. The findings expand the ocular phenotype of Proteus syndrome and encourage early assessment to identify any incipient ocular abnormalities.

The Flavonoid Kaempferol Ameliorates Streptozotocin-Induced Diabetes by Suppressing Hepatic Glucose Production.

In diabetes mellitus, the excessive rate of glucose production from the liver is considered a primary contributor for the development of hyperglycemia, in particular, fasting hyperglycemia. In this study, we investigated whether kaempferol, a flavonol present in several medicinal herbs and foods, can be used to ameliorate diabetes in an animal model of insulin deficiency and further explored the mechanism underlying the anti-diabetic effect of this flavonol. We demonstrate that oral administration of kaempferol (50 mg/kg/day) to streptozotocin-induced diabetic mice significantly improved hyperglycemia and reduced the incidence of overt diabetes from 100% to 77.8%. This outcome was accompanied by a reduction in hepatic glucose production and an increase in glucose oxidation in the muscle of the diabetic mice, whereas body weight, calorie intake, body composition, and plasma insulin and glucagon levels were not altered. Consistently, treatment with kaempferol restored hexokinase activity in the liver and skeletal muscle of diabetic mice while suppressed hepatic pyruvate carboxylase activity and gluconeogenesis. These results suggest that kaempferol may exert antidiabetic action via promoting glucose metabolism in skeletal muscle and inhibiting gluconeogenesis in the liver.

Bringing Open Data to Whole Slide Imaging.

Faced with the need to support a growing number of whole slide imaging (WSI) file formats, our team has extended a long-standing community file format (OME-TIFF) for use in digital pathology. The format makes use of the core TIFF specification to store multi-resolution (or "pyramidal") representations of a single slide in a flexible, performant manner. Here we describe the structure of this format, its performance characteristics, as well as an open-source library support for reading and writing pyramidal OME-TIFFs.

Kaempferol ameliorates hyperglycemia through suppressing hepatic gluconeogenesis and enhancing hepatic insulin sensitivity in diet-induced obese mice.

Obesity-associated insulin resistance (IR) is a major risk factor for developing type 2 diabetes and an array of other metabolic disorders. In particular, hepatic IR contributes to the increase in hepatic glucose production and consequently the development of fasting hyperglycemia. In this study, we explored whether kaempferol, a flavonoid isolated from Gink go biloba, is able to regulate hepatic gluconeogenesis and blood glucose homeostasis in high-fat diet-fed obese mice and further explored the underlying mechanism by which it elicits such effects. Oral administration of kaempferol (50 mg/kg/day), which is the human equivalent dose of 240 mg/day for an average 60 kg human, significantly improved blood glucose control in obese mice, which was associated with reduced hepatic glucose production and improved whole-body insulin sensitivity without altering body weight gain, food consumption or adiposity. In addition, kaempferol treatment increased Akt and hexokinase activity, but decreased pyruvate carboxylase (PC) and glucose-6 phosphatase activity in the liver without altering their protein expression. Consistently, kaempferol decreased PC activity and suppressed gluconeogenesis in HepG2 cells as well as primary hepatocytes isolated from the livers of obese mice. Furthermore, we found that kaempferol is a direct inhibitor of PC. These findings suggest that kaempferol may be a naturally occurring antidiabetic compound that acts by suppressing glucose production and improving insulin sensitivity. Kaempferol suppression of hepatic gluconeogenesis is due to its direct inhibitory action on the enzymatic activity of PC.

Pharmacologic management of glaucoma in childhood.

An evidence-based review of the drugs available for the medical management of childhood glaucoma is presented; almost all of the drugs are not licensed for use in children. Despite this, most topical drugs are safe; however, there are some significant exceptions, such as brimonidine, which may cause apnea, among other life-threatening adverse events, in infants. Broad families of drugs are available including topical adrenoceptor antagonists, topical and systemic carbonic anhydrase inhibitors, prostaglandin analogs, adrenoceptor agonists, parasympathomimetics, and combination preparations. These drugs help to reduce intraocular pressure by reducing aqueous production or increasing the outflow facility. The variety of anti-ocular hypertensive medications for childhood glaucoma has increased in recent years. The vast majority of data on these medications are from adult studies but each year more experience of their use in pediatric glaucoma is gained. In general, topical treatment is well tolerated; however, the prescribing clinician and carers should be aware of potential adverse effects and how they may present.

Evaluation of whether intracameral dexamethasone predisposes to glaucoma after pediatric cataract surgery.

PURPOSE: To evaluate the effect of intracameral dexamethasone during pediatric cataract surgery on the incidence of postoperative glaucoma. SETTING: Clinical and Academic Department of Ophthalmology, Great Ormond Street Hospital, London, United Kingdom. DESIGN: Retrospective case series. METHODS: This case-note review comprised all infants who had cataract surgery with intraocular lenses between January 1, 2007, and December 31, 2008, and were given preservative-free intracameral dexamethasone intraoperatively. The definition of glaucoma was an intraocular pressure (IOP) of 21 mm Hg or greater on more than 2 occasions or moderate or firm digital IOP with 1 of the following: myopic shift, increased cup-to-disc ratio, increased horizontal corneal diameter, or corneal edema. RESULTS: Eighteen patients (24 eyes) were included. The median age at surgery was 3 months (mean 4 months ± 3 (SD); range 1 to 11 months). The median follow-up was 38 months (mean 34 ± 10 months; range 20 to 48 months). In 4 eyes, transient postoperative antihypertensive medication was used; however, no eye developed glaucoma during the follow-up period. Fifteen eyes had a second procedure to clear the visual axis due to posterior visual axis opacification a mean of 6.4 ± 3.5 months postoperatively (median 4.8 months; range 3.5 to 14.5 months); however, no eye developed anterior membranes. CONCLUSION: Intracameral preservative-free dexamethasone in infantile cataract surgery did not seem to cause an increased risk for glaucoma and appeared to protect against anterior membrane formation.

Do reducing regimens of fluorometholone for paediatric ocular surface disease cause glaucoma?

BACKGROUND/AIMS: Although fluorometholone (FML) is considered a steroid of minimal ocular penetration, reports in children have shown dose-dependent intraocular pressure (IOP) rise. The authors aimed to assess whether reducing regimens of FML for paediatric ocular surface disease have sustained clinically significant ocular hypertensive effects. METHODS: Retrospective case-note review. Glaucoma was defined as an IOP of ≥ 21 mm Hg on at least two occasions or, in young children, moderate/firm digital IOP with one of the following: myopic shift, increased cup:disc ratio or corneal oedema. Exclusion criteria were other concurrent steroids or pre-existing optic nerve disease. RESULTS: 107 cases were included. The median age was 6 years (range 3 months to 17 years). The commonest indication for FML was blepharo-kerato-conjunctivitis. The maximal frequency prescribed was four times a day, gradually reduced to once weekly in cases of long-term treatment. The mean total number of eye-drop applications was 228 over a mean time span of 9 months. Post-FML IOP was formally documented in 51/107 casenotes (median age 6.85 years, range 4 months to 16 years) and it was <19 mm Hg in all cases. 56 cases did not allow IOP measurement (median age 5.9 years, range 3 months to 17 years), but none met the glaucoma definition. CONCLUSIONS: In this cohort, reducing regimens of FML proved to be a safe anti-inflammatory treatment in terms of avoiding steroid-induced glaucoma.

Metadata matters: access to image data in the real world.

Data sharing is important in the biological sciences to prevent duplication of effort, to promote scientific integrity, and to facilitate and disseminate scientific discovery. Sharing requires centralized repositories, and submission to and utility of these resources require common data formats. This is particularly challenging for multidimensional microscopy image data, which are acquired from a variety of platforms with a myriad of proprietary file formats (PFFs). In this paper, we describe an open standard format that we have developed for microscopy image data. We call on the community to use open image data standards and to insist that all imaging platforms support these file formats. This will build the foundation for an open image data repository.

On the measurement of human osteosarcoma cell elastic modulus using shear assay experiments.

This paper presents a method for determining the elastic modulus of human osteosarcoma (HOS) cells. The method involves a combination of shear assay experiments and finite element analysis. Following in-situ observations of cell deformation during shear assay experiments, a digital image correlation (DIC) technique was used to determine the local displacement and strain fields. Finite element analysis was then used to determine the Young's moduli of HOS cells. This involved a match of the maximum shear stresses estimated from the experimental shear assay measurements and those calculated from finite element simulations.