bluuebunny/crossref_metadata_2025 huggingface dataset:
Refractive surgery in glaucoma
Authors: Vastardis Iraklis
Published: December 2019

Laser‐assisted refractive corrections, phakic IOL implantations and refractive Lens exchange constitute a large part of the ophthalmic surgeries that take place every year. According to many surveys the incidence of glaucoma is increasing steadily over time worldwide. It is not uncommon today that glaucoma patients or patients unaware of their condition seek consultation for refractive surgery. As a result, a significant number of patients with altered corneal properties is emerging. These patients will require glaucoma follow‐up and probably additional surgery in the future. The reshaped post refractive surgery cornea poses a challenge in the diagnosis, follow‐up, and management of glaucoma patients for the physician. This presentation highlights the do's, don'ts and pitfalls when consulting or treating patients with these characteristics.
Influence of the complement system on corneal wound healing
Authors: Brockmann Tobias
Published: December 2019

Degenerative corneal disorders, which are associated to a severe loss of visual acuity very often are the result of misguided angiogenesis or wound healing/fibrogenesis; and thereby are the response to ischemic of inflammatory processes. Today, there are no causal therapeutic approaches for the treatment of fibrotic eye disorders. Hence, the aim of this project is to investigate the Influence of the complement system on the myofibroblast activation during corneal wound healing. Therefore, we analyzed molecular mechanisms of human specimens and performed cell culture and animal experiments to identify involved key processes. In human tissues we were able to identify a considerable complement activation in both, sterile and non‐sterile keratopathies. While the classical pathway was predominant in non‐sterile keratopathies, the alternative pathway was involved in sterile keratopathies. Based on our data from cell culture and animal experiments, we identified the central importance of complement factors C5 and C3 with their cleavage products during corneal wound healing and fibrogenesis. Thereby, our findings raised new insights and a better understanding of fundamental pathomechanisms in corneal wound healing that refer to new therapeutic concepts. In a first therapeutic approach, we were able to demonstrate anti‐fibrotic effects of complement anaphylatoxin (C3a/C4a/C5a)‐binding peptides in a model of corneal alkaline burns in mice. Thereby, less corneal fibrosis, using the clinical Cowell score; and distinctive gene‐ and proteomic‐expression profiles were revealed. In summary, complement anaphylatoxin (C3a/C4a/C5a) binders might pave the way for effective therapies of fibrotic eye disorders.
Agonistic beta2‐adrenergic autoantibodies in glaucoma
Authors: Hohberger Bettina
Published: December 2019

Glaucoma disease has a multifactorial pathogenesis with autoimmune components. Agonistic autoantibodies against β2‐adrenergic receptor autoantibodies (β2‐AAb) were observed in sera of patients with glaucoma and ocular hypertension, yet not in normal subjects. As data of a clinical proof‐of‐principle study showed that intraocular pressure (IOP) decreased after elimination of β2‐AAb by immunapharesis, a potential link to IOP was proposed. A specific blockade of these β2‐AAb could potential result in a novel medical strategy of glaucoma therapy.
Immune modulation following keratoplasty‐current and future aspects
Authors: Pleyer Uwe
Published: December 2019

Penetrating keratoplasty (pkp) has definitely its paradoxes. It has been the first successful transplantation in man and is with approx. 100 000 grafts/year easily the most frequent allograft in human medicine. At the same time, it is still the least understood form of transplantation in respect to its biology. It is both, the most successful as well as probably the most underestimated procedure regarding its risks in clinical transplantation. Indeed, the common assumption, that pkp is a safe procedure with favourable prognosis. This may have hindered more intensive efforts of research in this field. There are still limitations to corneal transplantation, and allograft rejection still poses the greatest challenge. In the last two decades, graft survival has greatly improved by the introduction of efficient immunosuppressive drugs. This lecture aims to highlight the most novel and successful strategies to achieve a better outcome of pkp, e.g. the use of mesenchymal stem cells and tolerance induction via regulatory T cells.
Radiation microangiopathy: new insights from clinical and imaging observations
Authors: Zografos Leonidas
Published: December 2019

Radiation induced maculopathy is a complex disorder resulting from the disruption of the outer and inner blood retinal barriers, in association with a vaso‐occlusive micro‐angiopathy. The retinal edema is observed and analyzed with the combination of the b‐Mode OCT, OCT en face and fluorescein angiophraphy. The vaso‐occlusive micro‐angiopathy is evaluated and quantified with OCT angiography. The surface of the non‐flow area and the circumference of the superficial capillary plexus as well as the status of the deep capillary plexus are taken in account in therapeutic decision with anti‐VEGF drugs.
Optic nerve complications after irradiation
Authors: Matet Alexandre
Published: December 2019

Optic neuropathy is a dramatic complication of ocular irradiation, usually leading to complete visual loss. This presentation will review the putative mechanisms, including direct neurotoxicity and indirect optic nerve head ischemic damage secondary to radiation microangiopathy; the spectrum of clinical manifestations; and available therapies for optic nerve complications after ocular irradiation.
Surgical management of neurotrophic keratopathy
Authors: Shortt Alex
Published: December 2019

Surgical treatment of neurotrophic keratopathy (NK), is indicated in advanced disease (stages 2 and 3) refractory to medical management. The objective is to prevent stromal involvement and to prevent corneal perforation.

The cornerstone of surgical therapy is tarsorrhaphy which narrows the palpebral fissure and decreases the area of exposed cornea. It can be temporary or permanent and partial or complete. An alternative to surgical tarsorrhaphy is botulium A toxin injection into the upper lid. Other surgical options are amniotic membrane transplantation to cover the epithelial defect (stage 2) or corneal ulcer (stage 3) and punctal occlusion to increase the amount of tears and improve lubrication. Corneal perforation, the ultimate sight threatening complication of NK, can be managed using cyanoacrylate glue or in larger defects a tectonic keratoplasty. Conjunctival flap may also be indicated in impending perforation. Outcomes of penetrating or lamellar corneal transplants in neurotrophic keratopathy are very poor. Direct neurotization of the cornea using branches of the contralateral ophthalmic division of the trigeminal nerve is difficult to perform but preserves cosmesis and can restore function.
Proteomics and personalized medicine in eye research and ophthalmology
Authors: Uusitalo Hannu
Published: December 2019

Proteomics is a novel option to detect biomarkers and drugable targets of various eye diseases. It can be used in experimental studies to study pathological processes as well as to detect clinically meaningful biomarkers and end point. It can be performed by using different specimens ranging from non‐invasively obtained tear samples and impression cytologic specimens to biopsies and various types of cell samples. Tear samples reflects not only the state of ocular surface but also that of other ocular structures or systemic state of the human body. Biopsies of ocular tissues are targeted way to detect various biological processes involved in eye diseases and processes involved in them like Inflammation, wound healing and angiogenesis. These are vital processes involved in the defense mechanisms of the human body and pathogenesis of many eye diseases, thus having potential to be in the development on novel therapies for eye diseases. These mechanisms are also important factors in ocular surgeries e.g. corneal, vitreoretinal and glaucoma surgery and thus a way to improve their success. In the future, proteomic biomarkers have a great potential to be tools of personalized medicine in choosing the best therapeutic options for each individual patient and to improve the cost‐effectiveness of the health care.
DALK or PKP? ‐ Surgical management of keratoconus
Authors: Seitz Berthold
Published: December 2019

Since 2010, more than 1300 patients have been registered in our Homburg Keratoconus Center HKC. Major objectives include (1) aetiology, (2) earliest diagnosis and (3) stage‐related treatment options. Excimer laser assisted DALK is a good option for skilled microsurgeons in case of good endothelium and lack of predescemetal scars offering visual acuity results of 20/25 or 20/20 when Descemet membrane is indeed exposed. In case of nonexposure of Descemet membran and/or in case of perforation conversion to excimer laser assisted PKP can be performed readily without disadvantages for the typically young patient.

Central round 8.0 or 8.5 mm excimer laser assisted PKP with double‐diagonal cross‐stitch suture is still state‐of‐the‐art in advanced keratoconus – especially after corneal hydrops. Nonmechanical excimer laser trephination results in (1) lower astigmatism, (2) higher regularity of topography and (3) better visual acuity. In contrast, femtosecond laser assisted PKP demanding applanation and deformation of the cone during suction, results in decentration and noncongruent shapes of donor and host intraoperatively as well as very high astigmatism after entire suture removal – thus to be considered the „excitement of yesterday“.
Aniridia‐ an example of multidisciplinary approach for research, collaboration and guidelines development
Authors: Bremond‐Gignac Dominique
Published: December 2019

Aniridia disease is a congenital rare eye disease involving both the anterior and posterior segment inducing low vision. As aniridia involves anomalies of different part of the eye all ophthalmic subspecialties are concerned. Aniridia related keratopathy, dry eye, glaucoma, anterior segment fibrosis are included for anterior segment specialists. Foveal hypoplasia, optic nerve hypoplasia, posterior segment fibrosis are included for posterior segment. In addition congenital aspects and nystagmus involves pediatric subspecialty and low vision. The diversity of ERN‐EYE Scientific meetings, collaboration with patients, registries and guidelines are being developed. Our French guidelines accredited by HAS (French Health Authority) are used with other guidelines from other two European countries to create a European consensus and guidelines physicians and for patients.
Impact of systemic hypertension on retinal and choroidal microvasculature using OCT Angiography
Authors: Chua Jacqueline
Published: December 2019

In this cross‐sectional study, we measured the retinal and choroidal microvasculature using the optical coherence tomographic angiography (OCTA) in 77 adults (n = 153 eyes) with systemic hypertension (mean [SD] age, 58 [9] years; 49% women; 23% poorly controlled BP) who are without ocular diseases and determined correlations with systemic vascular risk factors. Data on 24‐hr ambulatory blood pressure (BP) monitoring, serum creatinine, and urine microalbumin/creatinine ratio (MCR) were collected. Estimated glomerular filtration rate (eGFR) was calculated based on CKD‐EPI Creatinine Equation. OCTA imaging (6 × 6 mm macular scans; AngioVue) with quantitative retinal capillary densities (superficial and deep vascular plexuses; SVP and DVP) and choriocapillaris flow voids (area, size and number) were obtained. Linear regression was used to investigate the association of risk factors with microvascular analysis. Higher systolic BP was correlated with sparser retinal capillary density (β = −0.23, −0.44 to −0.02) and smaller areas of flow voids (β = −0.13, −0.24 to −0.02). Also, higher diastolic BP was correlated with flow voids that were smaller in individual size (β = −0.18, −0.34 to −0.02) but more numerous (β = 13.89, 0.61–27.17). Lower eGFR was correlated with sparser retinal capillary density (β = 6.42, 1.25–11.60) whereas renal parameters were not associated with flow voids. In patients with hypertension, higher BP appeared to cause retinal capillary dropout but increase blood flow in the choriocapillaris, which needs to be further investigated. Changes in the retinal microvasculature may reflect kidney function, which highlights the potential of using the OCTA to study early systemic microvascular changes.
Regulatory consideration: the differences between medical product and drug development
Authors: Schmetterer Leopold
Published: December 2019

In ophthalmology both medical devices and drugs are widely used. Although intuitively the difference between medical device and drug seems obvious, the classification is sometimes challenging. Development plans need to be tailored differently between medical devices and drugs regarding the primary intent and purpose. Accordingly, approval process varies significantly between the two ways of development. Essentially medical devices are defined as agents that do not achieve their primary intended purpose through chemical action in the body. However, exceptions may occur in certain indications such as dry eye disease. The talk will summarize the regulatory procedures, differences between European and US regulatory processes and provide some examples from ophthalmology.
The Franceschetti memorial library
Authors: Franceschetti Albert
Published: December 2019

Adolphe Franceschetti (1896‐1968) was not only a great Swiss ophthalmologist and geneticist, but also a punctilious specialist who would not quote a publication he had not seen. This led him to enrich the library of the Geneva Department of Ophthalmology with various series of journals he personally bought. When asked by professor Wessely's widow to help sell her late husband's library, he bought it himself, thus completing his own personal library. And upon retiring in 1966, he housed the library in a wing he had added to his house for the purpose. After his death in 1968, the library was continued by his son, also an ophthalmologist, and is now housed in the Chateau de Vétraz‐Monthoux, a manor in the surroundings of Geneva. The library contains most of the world's journals of ophthalmology and related specialties, practically all starting from their very first issue, and elegantly bound in over 16 000 volumes.To this must be added the full collection of Professor Franceschetti's reprints and those he received, plus a unique collection of all the 19th century reprints of dermatology, that had once belonged to professor Jadassohn's, a famous dermatologist form Bern, Switzerland, as well as the reprints of professor Jadassohn's works.. The newly updated catalogue is available on www.library-francescetti.com.The problem of such a library, as it is now the case, is its future, as it needs to find an institution that could assure its perenniality and the certainty that it will continue to be of use to scientists and students.
Retinal degeneration in Parkinson's disease
Authors: Cuenca NIcolás
Published: December 2019

Visual dysfunctions that Parkinson disease (PD) patients suffer are some of the first signs of the pathology. The aim of this work is to characterize some of the cellular alterations that occur in PD retinas and could lead to the reported visual impairments and also to determine if the retina can be used as an early biomarker for Parkinson disease. Wholemount retinas from PD and controls were immunostained using antibodies against p‐α‐synuclein, tyrosine hydroxylase and calretinin. Dopaminergic cells morphology, density and number of synaptic contacts with AII amacrine cells was established. Cells in the ganglion cell layer were immunostained and cell density was calculated. Microglia activation and gliosis were analyzed in retina and optic nerves. Posphorylated‐α‐synuclein was found in the retina within ganglion cells, axons, dendrites and in structures resembling Lewy Bodies. P‐α‐synuclein and Lewy bodies density significantly correlated between retina and brain. Dopaminergic cells in PD and synaptic contacts with AII amacrines were diminished, indicating alterations in the dopaminergic circuitries. Optic nerve remodeling and gliosis were found in PD. PD affects different cells and circuitries of the retina in a way that may explain some of the visual alterations reported in patients. Ganglion cell degeneration and optic nerve remodeling events in PD may explain the OCT layers thinning described in PD patients. The significant p‐α‐synuclein correlation suggests that the synucleinopathy occurs in the retina in a way analogous to the brain and thus, the retina could be considered as an early biomarker in Parkinson disease. Support: Michael J. Fox Foundation for Parkinson’s Research; Generalitat Valenciana Prometeo/2016/158, MINECO‐FEDER‐BFU2015‐67139‐R; Instituto Carlos III (RD16/0008/0016); MECD FPU 14/03166.
Retinal function in photoreceptor degenerations
Authors: de la Villa Pedro , de la Villa Pedro
Published: December 2019

Photoreceptor degeneration takes place in a group of inherited retinal dystrophies. In most cases, retinal degeneration courses with the dysfunction and death of photoreceptors, leading to blindness. Currently there is not treatment for this disease. Our group has focused in the study of retinal function during photoreceptor degeneration, as a strategy for the development of neuroprotective approaches to extend the visual function independently of the inherited mutation. We have carried out a systematic study of retinal function and photoreceptor structural modifications along the neurodegenerative process. Single cell recordings and Electroretinogram responses have been recording on retinal tissue under degeneration. Correlation of cell function and retinal structure, as studied by immunocytochemistry and electron microscopy confirms the parallelism between visual function loss and photoreceptor degeneration.
Iron and Transferrin
Authors: Picard Emilie
Published: December 2019

Iron has a dual role. Essential for cellular functions, it enhances oxidative stress when it is in excess and under a labile form. Iron accumulation and iron balance dysregulation are observed in animal models of retinal degeneration. Recently, we observed iron overload in ocular fluids from retinal detachment patients and highly transferrin saturation. As therapeutic strategy, we used transferrin (TF), the physiological iron transporter and the second most abundant protein in the vitreous, to reduce iron overload and therefore preserve visual function. Ocular administration of TF was no toxic. By several delivery ways and in different animal models of retinal dystrophies, we demonstrated the beneficial effect of TF. Iron accumulation, inflammation, oxidative stress, edema and cell death were decreased and retinal histology and visual function were preserved. Control of iron impairment in retinal tissues may be a major therapeutic strategy. We highlight the therapeutic potential of Transferrin in retinal diseases preventing vision loss.
IC3D second edition: an update
Authors: Kivelä Tero
Published: December 2019

The International Committee for Classification of Corneal Dystrophies (IC3D) was created by the Cornea Society in Chicago in 2005 to revise the corneal dystrophy nomenclature. The initial group consisted of 15 corneal specialists and 2 ophthalmic pathologists from North America, Europe and Asia, chaired by Dr. Jayne Weiss. The first IC3D edition was published in 2008. Already 6 years later, sufficient new data had become available to begin revision of the IC3D by 13 original and 2 new corneal specialists and 1 original ophthalmic pathologist. The second edition was published in 2015. Like the first one it presents each dystrophy as a template with key characteristics and typical clinical images, but is now supplemented with typical anterior segment OCT and histopathologic images as well. The category of ‘Bowman layer dystrophies’ was replaced by ‘Epithelial–stromal TGFBI dystrophies’ and ‘Descemet Membrane and Endothelial Dystrophies’ was simplified to ‘Endothelial Dystrophies’ because Bowman and Descemet are acellular and secondarily affected. Congenital Hereditary Endothelial Dystrophy 1 (CHED1) was merged with posterior polymorphous dystrophy 1 (PPMD1). Posterior amorphous corneal dystrophy (PACD) was found to be caused by a joint deletion of keratocan (KERA), lumican (LUM), decorin (DCN), and epiphycan (EPYC) genes. After publication of the second IC3D, epithelial recurrent erosion dystrophy (ERED) has been linked with COL17A1 mutations across the world, and the so called ‘variant Thiel‐Behnke dystrophy’, that was dubious, was found to be identical with ERED. The corneal dystrophy field continues to develop, making a third edition likely in the future.
Corneal recurrent erosions dystrophy in citizens and migrants in Finland
Authors: Turunen Joni
Published: December 2019

The epithelial recurrent erosion dystrophy (ERED) is a rare autosomal dominant corneal disease. Recently, mutations in collagen type XVII, alpha 1 (COL17A1) gene were identified as the cause of ERED. We have identified four Finnish families and one Armenian family with recurrent erosions and a dominant inheritance pattern. Affected patients reported recurrent corneal erosions beginning at the age of 4–12 years. The frequency of erosions decreased in adult age. Corneal scarring and anterior stromal opacities with varying degree were observed. The visual acuity of some patients slowly deteriorated. Next‐generation exome sequencing was performed in seven affected individuals from the five families focusing on the large COL17A1 gene. Sequencing analysis revealed that all seven patients carried a known synonymous splice‐altering variant c.3156C>T. Furthermore, five more family members were studied with Sanger sequencing. All twelve patients carried the same c.3156C>T variant. The variant was not present in gnomAD database including of 12,562 Finns. A genealogical analysis revealed that in one Finnish family the variant originated from Sweden. The variant c.3156C>T in COL17A1 is reported previously in English, American, Thai, New Zealand, and Tasmanian families with ERED. Our finding of the same variant in yet two other populations strengthens the evidence that this variant is the most frequent cause of ERED. The c.3156C>T codon seems to be a hot spot for recurrent mutations.
Can we avoid surgey? ‐ Crosslinking in the treatment of keratoconus
Authors: Zsolt Nagy Zoltán
Published: December 2019

Crosslinking is one of the recent effective treatments for keratoconus. The aim is to strengthten the biomechanical stability of the keratoconic eye by increasing the crosslinks between the collagen lamellae. We have been performing corneal CXL for 10 years in the Department of Ophthalmology, Semmelweis University, Budapest. The progression of the ectasia was succesfully stopped in most of the cases. In advanced cases CXL was found to be useful also before corneal transplant procedures as well. Details will be presented during the course.
Detecting structural progression
Authors: Tatham Andrew
Published: December 2019

Detecting and measuring rates of progression is central to glaucoma management with optical coherence tomography (OCT) playing an increasingly important role. The objective of this session is to summarise the latest evidence regarding the use of OCT for assessment of progression in glaucoma. Topics covered will include; the role of retinal nerve fibre layer (RNFL), optic nerve head and macula imaging; trend and event‐based progression analysis; the effect of disease severity on progression analysis; and methods of combining information from OCT and visual fields. The importance of differentiating true change from age‐related changes will also be discussed, in addition to the limitations of current imaging technology. Although OCT is now widely used measure glaucoma progression, the clinical relevance of these changes depends on their relationship to visual function. The session will conclude by examining the relationship between structural changes on OCT and measures of visual function.
Optics: The various speeds of lights 1
Authors: Mark Harry
Published: December 2019

Optics: The various speeds of lights 1 Ophthalmologists are naturally interested in keeping up with physical optics aside from the simple optical needs of practice. By measuring the periods of Jupiter's satellite Ole Roemer determined that the speed of light was higher when approaching and lower when receding from Jupiter then when at a steady distance from it. By measuring the angle which light from a star forms with an observer moving perpendicular to it James Bradley determined tat the speed of light was higher when approaching the vertical, and lower when receding from it than when positioned directly under it. By determining that the speed of light did not change when both its source and its observer were at a steady distance from one another and moving forward uniformly on the same platform, Albert Michelson conformed that light's motions were no different than those of any other motion. 1. Mark H.H. Fundamental Optics. Cambridge Scholars Publishing, Cambridge. 2019.
Beware the cat! Toxoplasma & co.
Authors: Carreño Ester
Published: December 2019

Ocular toxoplasmosis is the most common posterior uveitis. However atypical forms, such as those associated with severe occlusive vasculitis or mimicking acute retinal necrosis are a diagnostic challenge. The aim of this presentation id to help in the management and diagnosis of classic toxoplasma chorioretinitis and its more atypical presentations.
The role of simulators in future education and qualification in ophthalmology
Authors: Grupcheva Christina
Published: December 2019

Ophthalmology is one of the specialties that require very special skills because of the delicate and very fine structure of the eye and its adnexa. Today we operate utilizing not only microscopes but also 3 D systems. The skills required are not just difficult to acquire, but also complicated to sustain. Moreover, training in real patients is challenging from regulatory, ethical, moral, emotional and many other reasons. Therefore, utilizing simulators for training and CME is and opportunity with excellent perspective. Currently there are number of centers in Europe that implement simulators for ophthalmology training, however, there is no guideline for simulator training, except for Royal College of Ophthalmology in UK. The purpose of the presentation is to highlight pros and cones in simulation training and discuss the opportunities for improvement of the skills of beginner and established surgeon. Never‐the‐less, simulation training is the future, and ophthalmology educators must look for opportunities how to optimize and improve the complicated learning process for trainees at all levels.
Treatment approaches for radiation maculopathy and retinopathy
Authors: Isabel Riechardt Aline
Published: December 2019

Today it is possible to irradiate tumours, which would have been enucleated in the past and in addition remain high local tumor control rates. This is a consequence of our increasing understanding of irradiation‐induced side effects. The development of radiation‐induced maculopathy and retinopathy remain one of the most significant risk factors for visual impairment and secondary enucleation after irradiation. Therefore, it is essential to identify patients at risk and to offer them an appropriate treatment at the right time. The use of ultra‐wide field angiography offers us the possibility to detect early stages of peripheral ischemia to sufficiently treat patients with pan‐retinal photocoagulation. The consequent use of intravitreal VEGF‐inhibitors and corticosteroids gives us the opportunity to impede or at least delay the development of visual impairment due to radiation maculopathy. If possible, one should already try and spare or at least reduce the dose to vulnerable structures without compromising the local tumor control, when choosing the source of irradiation or during the planning procedure.
Human case
Authors: Leroy Bart P
Published: December 2019

A clinical case in ophthalmic genetics will be shown. Details regarding phenotype and genotype will be presented in an informative manner.
Neutrophils as an important pathophysiologic cellular component in the onset of AMD
Authors: Sinha Debasish
Published: December 2019

Vision loss from age‐related macular degeneration (AMD) is an expanding, major unmet problem due to the aging population worldwide. Inflammation has emerged as a potential cause of AMD, but how inflammation contributes to vision loss in AMD remains controversial despite intensive study around the world. Herein, we identify inflammatory signals that drive neutrophil infiltration into the retinas of early AMD patients and the Cryba1 conditional knockout mouse model that mimics an early AMD‐like phenotype. Specifically, we observed increased levels of IFNλ in early AMD that triggered neutrophil activation and lipocalin‐2 (LCN‐2) upregulation in these cells. NOD‐SCID immune‐deficient mice were injected intravenously with IFNλ activated bone marrow‐derived normal neutrophils labeled with red CMTPX dye. Ribbon‐scanning confocal microscopy (RSCM) of benzyl alcohol benzyl benzoate (BABB) cleared eyes, showed homing of neutrophils into the eye. In contrast, mice injected with IFNλ activated LCN‐2‐/‐ neutrophils showed fewer cells infiltrating the eye. LCN‐2 promotes inflammation and AMD‐like pathology by interacting with Disabled homolog2 (Dab2) and modulating integrin β1 levels to stimulate adhesion and transmigration of activated IL‐28R1 (IFNλ receptor) positive neutrophils into the retina. Inhibiting AKT2‐dependent signaling in the mouse model neutralizes IFNλ inflammatory signals, reducing LCN‐2‐mediated neutrophil infiltration into the retina and reversing early AMD‐like phenotype changes, thereby providing a potential therapeutic target for early AMD.
Comparison of xenon and gallium sources on the detection and mapping of lithium in Li‐containing materials by using ToF‐SIMS combined FIB‐SEM
Authors: DERMENCI K.B. , TESAŘOVÁ H. , ŠAMOŘIL T. , TURAN S.
Published: December 2019

Li can find itself a wide range of applications since it is the lightest metal. However, Li detection by microscopy‐based techniques is problematic because of the highly susceptible nature during electron beam irradiation. ToF‐SIMS is a versatile technique to detect Li but the detection of light materials is also problematic due to the large ion contaminated zone and low sputtering yield. By combining ToF‐SIMS with a recently launched Xe ion source FIB‐SEM, which has small ion contamination and high sputtering yield features, can produce more realistic data at near surface and below the surface region especially for the detection of lightweight materials such as Li. In this study, Li detection and mapping capabilities of ToF‐SIMS attached to the FIB‐SEM with Ga and Xe ion sources were discussed for Al incorporated Li7La3Zr2O12 solid electrolyte sample that contains Li and Al rich regions at triple junctions. In spite of smoother milling from Ga source, Xe performs more precisely in Li mapping. Low ion contaminated zone, high sputtering yield and low straggling obtained from Monte Carlo simulations are the main advantages of Xe ion sources. The Li detection efficiency for Xe is higher than Ga source discriminating the LiAlO2 phase placed at the triple junctions of grains and La2Zr2O7 regions placed at the outer side of LLZO neighbouring the LiAlO2 phase.

Lay Description

Li can find itself a wide range of applications since it is the lightest metal. However, Li detection by microscopy‐based techniques is problematic because of the highly susceptible nature during electron beam irradiation. ToF‐SIMS is a versatile technique to detect Li but the detection of light materials is also problematic due to the large ion contaminated zone and low sputtering yield. By combining ToF‐SIMS with a recently launched Xe ion source FIB‐SEM, which has small ion contamination and high sputtering yield features, can produce more realistic data at near surface and below the surface region especially for the detection of lightweight materials such as Li. In this study, Li detection and mapping capabilities of ToF‐SIMS attached to the FIB‐SEM with Ga and Xe ion sources were discussed for Al incorporated Li7La3Zr2O12 solid electrolyte sample that contains Li and Al rich regions at triple junctions. In spite of smoother milling from Ga source, Xe performs more precisely in Li mapping. Results were also supported from Monte Carlo simulations of ion‐atom interactions. The Li detection resolution of xenon is much higher than gallium source discriminating the LiAlO2 phase placed at the triple junctions of grains and La2Zr2O7 regions placed at the outer side of LLZO neighbouring the LiAlO2 phase.
Tau protein phosphorylation at Thr175 initiates fibril formation via accessibility of the N‐terminal phosphatase‐activating domain
Authors: Hintermayer Matthew A. , Volkening Kathryn , Moszczynski Alexander J. , Donison Neil , Strong Michael J.
Published: December 2019

One of the neuropathological hallmarks of the tauopathies is the formation of neuronal cytoplasmic inclusions and fibrils of microtubule‐associated tau protein (tau). The phosphorylation of Thr175 of tau (pThr175 tau) appears to be sufficient for fibril formation in vitro and in vivo, but the mechanism by which this initiates fibril formation is unknown. Using transient transfections of tau mutants into HEK293T cells, we determined that the phosphorylation of Thr175 leads to exposure of the tau N‐terminal phosphatase‐activating domain (PAD). The exposed PAD is known to interact with protein phosphatase‐1 (PP1) resulting in glycogen synthase kinase 3β (GSK3β) activation. In vivo, a single traumatic controlled cortical injury in rats also resulted in the phosphorylation of Thr175 and increased exposure of tau PAD followed by pathological tau fibril formation. Taken together, these data suggest that neurotoxicity may be precipitated by phosphorylation at Thr175 and subsequent tau PAD exposure, GSK3β activation and tau fibril formation.

image

Cover Image for this issue: doi: 10.1111/jnc.14767.
Four cases of Mayer–Rokitansky–Küster–Hauser syndrome treated via non‐surgical vaginal reconstruction using uterine cervical dilators
Authors: Kawasaki Akiko , Itagagi Hiroya , Tsumagari Ayako , Ijiri Hiroko , Yoshikawa Hiroyuki , Sato Toyomi
Published: December 2019

Vaginal creation is the standard treatment for Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome. Although non‐surgical method is recommended as a first‐line treatment in the American College of Obstetricians and Gynecologists guidelines for gynecological practice, it is not commonly performed in Japan. At our hospital, vaginal dilation using uterine cervical dilators (Hegar's dilator) is performed for patients with MRKH syndrome. We report four cases successfully treated with vaginal dilation. After the examination, patients were instructed to practice daily self‐dilation at home. The initiation size was No. 13 with 10.5‐mm diameter. After the vaginal cavity was dilated to a depth of 6 cm, the size of dilators was gradually increased until No. 30 with 25‐mm diameter in a tip and 28‐mm diameter in a trunk. The duration required to achieve the outcome was 5–22 months. All cases were successfully treated without any severe complication.
Progranulin promotes osteogenic differentiation of human periodontal ligament stem cells via tumor necrosis factor receptors to inhibit TNF‐α sensitized NF‐kB and activate ERK/JNK signaling
Authors: Chen Jing , Yu Miao , Li Xiao , Sun Qin‐Feng , Yang Cheng‐Zhe , Yang Pi‐Shan
Published: December 2019

Objective

To investigate the molecular mechanism of Progranulin (PGRN) in promoting osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) in inflammatory environment.

Background

Progranulin is an antagonist of tumor necrosis factor (TNF) receptors (TNFRs) and is known to promote inflammatory periodontal bone defect regeneration.

Methods

TNFR1‐ and TNFR2‐silenced hPDLSCs designed as hPDLSCs‐sh‐TNFR1 and hPDLSCs‐sh‐TNFR2 were cultured with osteoinductive medium containing TNF‐α and (or) PGRN. Immunofluorescence, quantitative real‐time PCR, and western blot were used to, respectively, detect expressions of TNFR1\TNFR2 and osteogenic differentiation markers as well as phosphorylation level in NF‐κB\MAPK‐related pathways.

Results

Immunofluorescence and real‐time PCR showed that TNFR1 and TNFR2 positively expressed in hPDLSCs. TNF‐α stimulation could significantly decrease the expressions of ALP and RUNX2 in hPDLSCs, whereas PGRN treatment could significantly enhance their expressions, and reverse TNF‐α‐mediated expression suppression of ALP and RUNX2 in hPDLSCs. In hPDLSCs‐sh‐TNFR1, TNF‐α mediated osteogenic inhibition decreased, but both TNF‐α + PGRN and alone PGRN significantly promoted expression of ALP and RUNX2. PGRN significantly enhanced expression of P‐ERK1/2 and P‐JNK, while corresponding inhibitors eliminated PGRN‐stimulated osteogenic differentiation. In hPDLSCs‐sh‐TNFR2, no significant difference existed in osteogenic markers and P‐JNK expression between the PGRN group and the control group. However, PGRN still activated P‐ERK1/2 expression. Besides, PGRN antagonized TNF‐α‐enhanced NF‐κB P65 expression.

Conclusion

Progranulin promotes osteogenic differentiation of hPDLSCs via TNFR1 to inhibit TNF‐α‐sensitized NF‐κB and via TNFR2 to activate JNK signaling. The mechanism by which PGRN activates ERK signaling remains to be explored.
Enhancing the hepatitis B care cascade in Australia: A cost‐effectiveness model
Authors: Xiao Yinzong , Howell Jessica , van Gemert Caroline , Thompson Alexander J. , Seaman Christopher P. , McCulloch Karen , Scott Nick , Hellard Margaret E.
Published: December 2019

If Australia is to successfully eliminate hepatitis B as a public health threat, it will need to enhance the chronic hepatitis B (CHB) care cascade. This study used a Markov model to assess the impact, cost and cost‐effectiveness of scaling up CHB diagnosis, linkage to care and treatment to reach national and international elimination targets for hepatitis B in Australia. Compared to continued current trends, the model calculated the difference in care cascade projection, disability‐adjusted life years (DALYs), costs and the incremental cost‐effectiveness ratio (ICER), of scaling up CHB diagnosis, linkage to care and treatment to reach: (a) Australia's 2022 national targets and (b) the WHO’s 2030 global targets. Achieving the national and WHO targets had ICERs of A$13 435 (A$10 236‐A$21 165) and A$14 482 (A$13 031‐A$25 641) per DALY averted between 2016 and 2030 in Australia, respectively. However, this excluded implementation and demand generation costs. The ICER for the National Strategy and WHO Strategy remained under A$50 000 per DALY averted if Australia spent up to A$328 or A$538 million, respectively, per annum (for 2016‐2030) on implementation and demand generation activities. Sensitivity analysis showed that cost‐effectiveness was predominately driven by the cost of CHB treatment and influenced by disease progression rates. Hence for Australia to reach the National Hepatitis B Strategy 2022 targets and WHO Strategy 2030 targets, it requires an improvement in the CHB care cascade. We estimated it is cost‐effective to spend up to A$328 million or A$538 million per year to reach the National and WHO Strategy targets, respectively.
A Bridge Too Far? Examining Bridging Assumptions in Common‐Space Estimations
Authors: Gray Thomas R. , Jenkins Jeffery A.
Published: December 2019

While most common‐space estimations rely upon members who served in both the House and Senate as “bridges” to scale the remaining members, this assumes that these “bridge members” do not change their preferences when they change chambers. Such an assumption conflicts with standard notions of representation, that is, that legislators’ votes reflect (at least to some degree) the wishes of their constituents. We examine the constancy of this common‐space voting assumption by focusing on a subset of House members who move to the Senate: those who come from statewide House districts. Using these members as the bridge actors—and thus bridging by constituency explicitly—in a one‐dimensional item response theory model, we find that the standard assumption of chamber switchers in common‐space estimations is technically, but immaterially, false. While there are statistically distinguishable differences in House and Senate voting records for chamber switchers, they are not sufficiently large to meaningfully undermine bridging.
Hydrothermal activity on the CV parent body: New perspectives from the giant Transantarctic Mountains minimeteorite TAM5.29
Authors: Nava J. , Suttle M. D. , Spiess R. , Folco L. , Najorka J. , Carli C. , Massironi M.
Published: December 2019

TAM5.29 is an extraterrestrial dust grain, collected on the Transantarctic Mountains (TAM). Its mineralogy is dominated by an Fe‐rich matrix composed of platy fayalitic olivines and clasts of andradite surrounded by diopside‐jarosite mantles; chondrules are absent. TAM5.29 records a complex geological history with evidence of extensive thermal metamorphism in the presence of fluids at T < 300 °C. Alteration was terminated by an impact, resulting in shock melt veins and compaction‐orientated foliation of olivine. A second episode of alteration at lower temperatures (<100 °C) occurred postimpact and is either parent body or terrestrial in origin and resulted in the formation of iddingsite. The lack of chondrules is explained by random subsampling of the parent body, with TAM5.29 representing a matrix‐only fragment. On the basis of bulk chemical composition, mineralogy, and geological history TAM5.29 demonstrates affinities to the CVox group with a mineralogical assemblage in between the Allende‐like and Bali‐like subgroups (CVoxA and TAM5.29 are rich in andradite, magnetite, and FeNiS, but CVoxA lacks hydrated minerals, common in TAM5.29; conversely, CVoxB are rich in hydrated phyllosilicates but contain almost pure fayalite, not found in TAM5.29). In addition, TAM5.29 has a slightly different metasomatic history, in between the oxidized and reduced CV metamorphic grades while also recording higher oxidizing conditions as compared to the known CV chondrites. This study represents the third CV‐like cosmic dust particle, containing a unique composition, mineralogy, and fabric, demonstrating variation in the thermal metamorphic history of the CV parent body(‐ies).
Minimum dietary diversity among women of reproductive age in urban Burkina Faso
Authors: Custodio Estefania , Kayikatire Francois , Fortin Sonia , Thomas Anne‐Claire , Kameli Yves , Nkunzimana Tharcisse , Ndiaye Biram , Martin‐Prevel Yves
Published: December 2019

Micronutrient malnutrition is a challenge for women of reproductive age, who are particularly vulnerable due to greater micronutrient needs. The minimum dietary diversity for women (MDD‐W) indicator is a micronutrient adequacy's proxy for those women, but little is known about its relation to other dimensions. We assessed MDD‐W and its association with other socioeconomic, food security and purchasing practices in urban Burkina Faso. We conducted multi‐stage cluster sampling in two main cities of Burkina Faso, stratified by type of district, and interviewed 12 754 women in the 2009‐2011 period. We obtained food consumption data through unquantified 24 hour recalls and computed MDD‐W as consuming at least five out of ten predefined food groups. We constructed multivariable regression models with sociodemographic and food security covariates. MDD‐W in urban Burkina Faso was 31%, higher in Ouagadougou (33%) than in Bobo‐Dioulasso (29%), and lower in unstructured districts. The most frequently consumed food groups were ‘all starchy', ‘vitamin A rich dark green leafy vegetables' and ‘other vegetables'. Household's expenses were associated with higher likelihood of MDD‐W, while the association with household food security indicators varied by year and type of district. Purchasing foods in markets and choosing the place of purchase based on large choice rather than proximity showed a positive association with the MDD‐W. Only one in three women in urban Burkina Faso reached the minimum dietary diversity, and although socioeconomic and food security variables had the greatest effect on MDD‐W, purchasing practices, like going to the market, also showed a positive effect.
Skin in the game: Epidermal molt as a driver of long‐distance migration in whales
Authors: Pitman Robert L. , Durban John W. , Joyce Trevor , Fearnbach Holly , Panigada Simone , Lauriano Giancarlo
Published: December 2019

Long‐distance migration in whales has historically been described as an annual, round‐trip movement between high‐latitude, summer feeding grounds, and low‐latitude, winter breeding areas, but there is no consensus about why whales travel to the tropics to breed. Between January 2009 and February 2016, we satellite‐tagged 62 antarctic killer whales (Orcinus orca) of four different ecotypes, of which at least three made short‐term (6–8 weeks), long‐distance (maximum 11,000 km, round trip), essentially nonstop, migrations to warm waters (SST 20°C–24°C), and back. We previously suggested that antarctic killer whales could conserve body heat in subfreezing (to −1.9°C) waters by reducing blood flow to their skin, but that this might preclude normal (i.e., continuous) epidermal molt, and necessitate periodic trips to warm waters for routine skin maintenance (“skin molt migration,” SMM). In contrast to the century‐old “feeding/breeding” migration paradigm, but consistent with a “feeding/molting” hypothesis, the current study provides additional evidence that deferred skin molt could be the main driver of long‐distance migration for antarctic killer whales. Furthermore, we argue that for all whales that forage in polar latitudes and migrate to tropical waters, SMM might also allow them to exploit rich prey resources in a physiologically challenging environment and maintain healthy skin.
Tit for Tat and Beyond: The Legendary Work of Anatol Rapoport
Authors: Kopelman Shirli
Published: December 2019

This article pays tribute to Anatol Rapoport. Rapoport’s contributions spanned scientific disciplines and included the application of mathematical models to biology and the social sciences, alongside metatheoretical work bridging semantics, ethics, and philosophy. Known for formulating the “Tit for Tat” strategy, his approach to game theory reflected a nuanced understanding of knowledge, wisdom, and ethics; the differences, for example, between modeling behavior—what works as an algorithm in a structured game—and solving complex human social interactions. While developing a science of human conflict, Rapoport focused on simple ideas to promote cooperation; his ultimate goal was to foster world peace. A career overview alongside testimonials by scholars and family provide a glimpse of Anatol Rapoport, the scientist and the person. The legacy and thinking of Anatol Rapoport continue to resonate and reverberate today whenever we conduct rigorous scholarship toward transforming conflict into peaceful harmony, whether among people or nations.