bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatocyte Concentrations of Indocyanine Green Reflect Transfer Rates Across Membrane Transporters
Authors: Cusin Fabien , Fernandes Azevedo Liliana , Bonnaventure Pierre , Desmeules Jules , Daali Youssef , Pastor Catherine M.
Published: September 2016

Perioperative imaging with indocyanine green (ICG) is developing to increase safety in dissecting anatomical structures during hepatobiliary surgery. Images obtained with the fluorescence camera rely on concentrations measured in liver regions of interest. However, how ICG sinusoidal uptake and hepatocyte elimination rates generate ICG hepatocyte concentrations is largely unknown. To investigate such issue and better understand the role of membrane transporters in generating ICG hepatocyte concentrations, we perfused ICG in livers isolated from normal livers. Whether the well‐known transporter inhibitor rifampicin modifies hepatocyte ICG concentrations was also studied. The dye has a very high and constant extraction ratio (96%) into hepatocytes. This persistent high extraction ratio generates a huge uphill concentration gradient across the sinusoidal membrane: from 5 μM (sinusoids) to 1600 μM (liver). When inside hepatocytes, ICG has low hepatocyte elimination (7 nmol/min.) and liver concentrations do not decrease much over time. Moreover, the tiny hepatocyte ICG efflux is mainly due to ICG return back to sinusoids (90%). Rifampicin slightly inhibits ICG uptake into hepatocytes and when inside hepatocytes blocks ICG efflux into bile canaliculi. In contrast, it increases ICG efflux back to sinusoids with significant decrease in ICG liver concentrations. Imaging with ICG in the perioperative period reflects the high hepatocyte concentrations and relies on the high extraction ratio across hepatocyte sinusoidal membrane. Although ICG concentrations are low in bile ducts, they are adequate for a good visualization and avoid bile duct injury.
Diet selection at three spatial scales: Implications for conservation of an endangered Hawaiian tree snail
Authors: Price Melissa R. , O'Rorke Richard , Amend Anthony S. , Hadfield Michael G.
Published: September 2016

Several recent studies suggest local adaptation in multiple taxa across Hawaii's steep environmental gradients. Restoration efforts in devastated tropical island ecosystems may be deficient if we lack an understanding of the interactions and dependencies in communities that occur along these gradients. Endangered Hawaiian tree snails are part of a snail–epiphyte–plant system where they graze fungi and other microbes on the leaf surface, a process difficult to observe using conventional techniques. Tree snails have undergone catastrophic decline due to introduced predators, removal by shell collectors, and human‐influenced habitat degradation. Prior to this study, little was known about the relationship among tree‐snails, their host plants, and the epiphytic microbes on which they feed. In this study, we identified scale‐dependent selection of substrates in Achatinella sowerbyana and Achatinella lila across the species’ ranges. We assessed: (1) within‐plant diet selection using high‐throughput DNA sequencing (micro‐scale); (2) among‐plant selection of tree host species (small‐scale); (3) and the influence of climate on this system (macro‐scale). Selection of substrates occurred at two scales: fungal communities in fecal samples differed in composition from those available on leaf surfaces; and at all sites, snail occurrence on Metrosideros polymorpha, a foundational forest plant, was significantly higher than expected based on availability. Habitat restoration efforts should focus on out‐planting of M. polymorpha, the preferred snail host tree, in degraded habitat. Fungal differences across sites suggest relocation efforts to predator‐free enclosures may be hindered by microbial shifts associated with geographic distance or differing environments.
Florivory and floral larceny by fly larvae decrease nectar availability and hummingbird foraging visits at Heliconia (Heliconiaceae) flowers
Authors: Missagia Caio C. C. , Alves Maria Alice S.
Published: September 2016

Insect larvae inhabit the corolla tubes of some Heliconia species (Heliconiaceae). In this study, we present the first evidence of the influence of these larvae on the pollination ecology of Heliconia plants. We provide experimental evidence that the flowers of Heliconia spathocircinata infested by flies have less nectar for pollinators and received fewer visits by hummingbird pollinators, in comparison with uninfested flowers.
CITED2 in breast carcinoma as a potent prognostic predictor associated with proliferation, migration and chemoresistance
Authors: Minemura Hiroyuki , Takagi Kiyoshi , Sato Ai , Takahashi Hikaru , Miki Yasuhiro , Shibahara Yukiko , Watanabe Mika , Ishida Takanori , Sasano Hironobu , Suzuki Takashi
Published: September 2016

CITED2 (Cbp/p300‐interacting transactivator, with Glu/Asp‐rich carboxy‐terminal domain, 2) is a member of the CITED family and is involved in various cellular functions during development and differentiation. Mounting evidence suggests the importance of CITED in the progression of human malignancies, but the significance of CITED2 protein has not yet been examined in breast carcinoma. Therefore, in the present study, we examined the clinical significance and the biological functions of CITED2 in breast carcinoma by immunohistochemistry and in vitro study. CITED2 immunoreactivity was detected in breast carcinoma tissues, and it was significantly higher compared to those in morphologically normal mammary glands. CITED2 immunoreactivity was significantly associated with stage, pathological T factor, lymph node metastasis, histological grade, HER2 and Ki‐67, and inversely correlated with estrogen receptor. Moreover, the immunohistochemical CITED2 status was significantly associated with increased incidence of recurrence and breast cancer‐specific death of the breast cancer patients, and multivariate analyses demonstrated CITED2 status as an independent worse prognostic factor for disease‐free and breast cancer‐specific survival. Subsequent in vitro experiments showed that CITED2 expression significantly increased proliferation activity and migration property in MCF‐7and S KBR‐3 breast carcinoma cells. Moreover, CITED2 caused chemoresistance to epirubicin and 5‐fluorouracil, but not paclitaxel, in these cells, and it inhibited p53 accumulation after 5‐fluorouracil treatment in MCF‐7 cells. These results suggest that CITED2 plays important roles in the progression and chemoresistance of breast carcinoma and that CITED2 status is a potent prognostic factor in breast cancer patients.
Age-related alterations in immune responses to West Nile virus infection
Authors: Montgomery R R
Published: September 2016

West Nile virus (WNV) is the most important causative agent of viral encephalitis worldwide and an important public health concern in the United States due to its high prevalence, severe disease, and the absence of effective treatments. Infection with WNV is mainly asymptomatic, but some individuals develop severe, possibly fatal, neurological disease. Individual host factors play a role in susceptibility to WNV infection, including genetic polymorphisms in key anti-viral immune genes, but age is the most well-defined risk factor for susceptibility to severe disease. Ageing is associated with distinct changes in immune cells and a decline in immune function leading to increased susceptibility to infection and reduced responses to vaccination. WNV is detected by pathogen recognition receptors including Toll-like receptors (TLRs), which show reduced expression and function in ageing. Neutrophils, monocyte/macrophages and dendritic cells, which first recognize and respond to infection, show age-related impairment of many functions relevant to anti-viral responses. Natural killer cells control many viral infections and show age-related changes in phenotype and functional responses. A role for the regulatory receptors Mertk and Axl in blood–brain barrier permeability and in facilitating viral uptake through phospholipid binding may be relevant for susceptibility to WNV, and age-related up-regulation of Axl has been noted previously in human dendritic cells. Understanding the specific immune parameters and mechanisms that influence susceptibility to symptomatic WNV may lead to a better understanding of increased susceptibility in elderly individuals and identify potential avenues for therapeutic approaches: an especially relevant goal, as the world's populating is ageing.
General, but not myeloid or type II lung epithelial cell, myeloid differentiation factor 88 deficiency abrogates house dust mite induced allergic lung inflammation
Authors: Anas A A , Yang J , Daan de Boer J , Roelofs J J T H , Hou B , de Vos A F , van der Poll T
Published: September 2016

Asthma is a highly prevalent chronic allergic inflammatory disease of the airways affecting people worldwide. House dust mite (HDM) is the most common allergen implicated in human allergic asthma. HDM-induced allergic responses are thought to depend upon activation of pathways involving Toll-like receptors and their adaptor protein myeloid differentiation factor 88 (MyD88). We sought here to determine the role of MyD88 in myeloid and type II lung epithelial cells in the development of asthma-like allergic disease using a mouse model. Repeated exposure to HDM caused allergic responses in control mice characterized by influx of eosinophils into the bronchoalveolar space and lung tissue, lung pathology and mucus production and protein leak into bronchoalveolar lavage fluid. All these responses were abrogated in mice with a general deficiency of MyD88 but unaltered in mice with MyD88 deficiency, specifically in myeloid or type II lung epithelial cells. We conclude that cells other than myeloid or type II lung epithelial cells are responsible for MyD88-dependent HDM-induced allergic airway inflammation.
Genetics of syndromic and non‐syndromic hereditary nail disorders
Authors: Bergqvist C. , Ramia P. , Abbas O. , Kurban M.
Published: September 2016

The nail is a unique epithelial skin appendage made up of a fully keratinized nail plate. The nail can be affected in several systemic illnesses, dermatological diseases, and inherited nail disorders. Nail dystrophies can present as isolated disorders or as a part of syndromes. Substantial progress has been achieved in the management and diagnosis of nail diseases; however, not much is known about the underlying molecular controls of nail growth. The homeostasis and development of the nail appendage depend on the intricate interactions between the epidermis and underlying mesenchyme, and comprise different signaling pathways such as the WNT signaling pathway. Digit‐tip regeneration in mice and humans has been a known fact for the past six decades; however, only recently the underlying biological mechanisms by which the nail organ achieves digit regeneration have been elucidated. Moreover, significant progress has been made in identifying nail stem cells and localizing stem cell niches in the nail unit. More fascinating, however, is the role they play in orchestrating the processes that lead to the regeneration of the digit. Further elucidating the role of nail stem cells and the signaling pathways driving epithelial–mesenchymal interactions in the nail unit might contribute to the development of novel therapeutic tools for amputees.
Baraitser–Winter cerebrofrontofacial syndrome
Authors: Yates T.M. , Turner C.L. , Firth H.V. , Berg J. , Pilz D.T.
Published: September 2016

Baraitser–Winter cerebrofrontofacial syndrome (BWCFF) (BRWS; MIM #243310, 614583) is a rare developmental disorder affecting multiple organ systems. It is characterised by intellectual disability (mild to severe) and distinctive facial appearance (metopic ridging/trigonocephaly, bilateral ptosis, hypertelorism). The additional presence of cortical malformations (pachygyria/lissencephaly) and ocular colobomata are also suggestive of this syndrome. Other features include moderate short stature, contractures, congenital cardiac disease and genitourinary malformations. BWCFF is caused by missense mutations in the cytoplasmic beta‐ and gamma‐actin genes ACTB and ACTG1. We provide an overview of the clinical characteristics (including some novel findings in four recently diagnosed patients), diagnosis, management, mutation spectrum and genetic counselling.
Effect of prosthetic restoration on implant survival and success
Authors: Rammelsberg Peter , Lorenzo‐Bermejo Justo , Kappel Stefanie
Published: September 2016

Purpose

The objective of this work was to evaluate the effect of prosthetic restoration on the survival of implants and on the incidence of implant‐related complications.

Material and methods

From a prospectively documented clinical study, 1569 implants placed in 630 patients (mean age 59.56 years) were evaluated. Selection criteria were a conventional loading protocol, prosthetic restoration with at least one follow‐up, and a minimum observation period of 9 months. Implants that failed before prosthetic restoration were excluded. The sample included 1345 tissue‐level implants and 104 bone‐level implants (Straumann), and 120 Replace implants (Nobel Biocare). The observation period ranged between 9 months and 11 years after prosthetic restoration (mean 4.0 years; SD 2.5). The implants were restored with single crowns (n = 557), fixed dental prostheses (n = 594), or removable dental prostheses (RDP) (n = 418). In the RDP group, 356 implants were restored with telescoping crowns, 22 with bar units 24 with bar joints, and 16 with locator attachments. The incidence of implant‐related complications and failures was analyzed by use of Kaplan–Meier survival curves. Cox regression analysis was used to identify possible risk factors.

Results

Twenty‐seven failures (1.8%; loosened or removed implants) were observed after prosthetic restoration; the incidence of failure was 3% for implants placed in males and 1% for implants placed in females. Other factors had no effect on the incidence of failure. Peri‐implantitis (n = 29) and marginal bone loss >2 mm without acute inflammation (n = 6) also resulted in a 4% incidence of severe implant‐related complications (62 of 1569; success 96%). Cox regression analysis revealed combined tooth–implant‐supported restorations as a significant risk‐reducing factor for severe implant‐related complications (hazard ratio, HR = 0.34; P = 0.04). There was, furthermore, a tendency toward a greater incidence of complications for implants restored with RDPs than for single crowns (P = 0.08). Other factors, for example location (anterior/posterior, maxilla/mandible), age, sex, or implant placement combined with bone augmentation, had no significant effect on the incidence of implant‐related complications (P values ranging between 0.16 and 0.94).

Conclusions

The type of support has a small but significant effect on implant prognosis. For detailed analysis of the effects of loading by different types of prosthetic restoration, larger sample sizes are required.
Ear health and hearing surveillance in girls and women with Turner's syndrome: recommendations from the Turner's Syndrome Support Society
Authors: Kubba H. , Smyth A. , Wong S.C. , Mason A.
Published: September 2016

Background

Turner's syndrome (TS) is a common chromosomal disorder, affecting one in 2000 newborn girls, in which part or all of one X chromosome is missing. Ear and hearing problems are very common in girls and women with TS. The aim of this review was to review the published literature to suggest recommendations for otological health surveillance.

Method

A keyword search of Ovid Medline was performed for published literature on the subject and evidence rated according to the GRADE criteria.

Results

Middle ear disorders are very common and persistent in girls and women with TS as are progressive sensorineural hearing loss and balance disorders.

Conclusions

Otolaryngologists should be aware of the high prevalence and challenging nature of all forms of ear disease in individuals with TS. Early intervention may offer benefits to health and education, and we advocate routine lifelong annual hearing screening in this group.
Effect of continuous positive airway pressure on liver enzymes in obstructive sleep apnea: A meta‐analysis
Authors: Chen Li‐Da , Lin Li , Zhang Liang‐Ji , Zeng Hui‐Xue , Wu Qi‐Yin , Hu Miao‐Feng , Xie Jian‐Jun , Liu Jian‐Nan
Published: September 2016

Background

Previous studies have suggested that obstructive sleep apnea (OSA) was associated with nonalcoholic fatty liver disease (NAFLD). However, the impact of OSA treatment using continuous positive airway pressure (CPAP) on liver enzymes remained controversial. This meta‐analysis was conducted to determine whether CPAP therapy could reduce liver enzyme levels.

Methods

Two reviewers independently searched PubMed, Cochrane library, Embase and Web of Science before December 2015. Information on characteristics of subjects, study design and pre‐ and post‐CPAP treatment of serum ALT and AST was extracted for analysis. A total of five studies with seven cohorts that included 192 patients were pooled into meta‐analysis.

Results

CPAP was associated with a statistically significant decrease on both ALT and AST levels in OSA patients (WMD = 8.036, 95% CI = 2.788–13.285, z = 3.00, P = .003 and WMD = 4.612, 95% CI = 0.817–8.407, z = 2.38, P = .017, respectively). Subgroup analyses indicated that CPAP therapy was more effective in OSA patients with treatment duration > 3 mo (WMD = 12.374, 95% CI = 2.727–22.020, z = 2.51, P = .012 for ALT and WMD = 7.576, 95% CI = 1.781–13.370, z =2.56, P = .010 for AST).

Conclusion

This meta‐analysis suggested that CPAP was associated with a statistically significant decrease on liver enzymes in OSA patients. Further large‐scale well‐designed RCTs with long‐term follow‐up are required to clarify this issue.
Sola Scriptura—A Hermeneutical Impossibility and a Doctrinal Necessity: Twenty‐One Theses
Authors: Henriksen Jan‐Olav
Published: September 2016

The following theses represent an attempt to delineate some of the contemporary basic conditions for maintaining the use of the sola Scriptura in the Lutheran churches. This must, I argue, be done without using it as a means for ignoring other types of information and experience than that which is contained in the Scriptures. I argue that sola Scriptura formulates what is necessary for salvation, but cannot be used to delineate or present all information that is necessary to live in the contemporary world and interpret all contemporary experience.
The Holy Spirit, Eco‐Justice, and an African Lutheran Response to Ecological Peril
Authors: Lugazia Faith K.
Published: September 2016

In response to the environmental degradation that is taking place right now in much of Africa—and in light of a traditional African emphasis on interdependence—this article seeks to provide an African Lutheran “eco‐pneumatological” contribution to the ongoing conversation about eco‐justice. To do so, it draws on classic Lutheran understandings of creation and grace, even as it calls for a more expanded—and more deeply biblical—understanding of the Holy Spirit's presence and activity throughout all of creation.
Social carry‐over effects underpin trans‐seasonally linked structure in a wild bird population
Authors: Firth Josh A. , Sheldon Ben C.
Published: September 2016

Spatial structure underpins numerous population processes by determining the environment individuals' experience and which other individuals they encounter. Yet, how the social landscape influences individuals' spatial decisions remains largely unexplored. Wild great tits (Parus major) form freely moving winter flocks, but choose a single location to establish a breeding territory over the spring. We demonstrate that individuals' winter social associations carry‐over into their subsequent spatial decisions, as individuals breed nearer to those they were most associated with during winter. Further, they also form territory boundaries with their closest winter associates, irrespective of breeding distance. These findings were consistent across years, and among all demographic classes, suggesting that such social carry‐over effects may be general. Thus, prior social structure can shape the spatial proximity, and fine‐scale arrangement, of breeding individuals. In this way, social networks can influence a wide range of processes linked to individuals' breeding locations, including other social interactions themselves.
Do 45% of College Students Lack Critical Thinking Skills? Revisiting a Central Conclusion of Academically Adrift
Authors: Lane David , Oswald Frederick L.
Published: September 2016

The educational literature, the popular press, and educated laypeople have all echoed a conclusion from the book Academically Adrift by Richard Arum and Josipa Roksa (which has now become received wisdom), namely, that 45% of college students showed no significant gains in critical thinking skills. Similar results were reported by Pascarella, Blaich, Martin, and Hanson after the publication of Arum and Roksa's book in 2011. However, these authors' statistical tests were conducted incorrectly, and therefore this 45% finding is fundamentally untrue. We demonstrate that a correct statistical analysis would have found that far fewer students show significant gains in critical thinking. However, this does not reflect on student learning; instead, it reflects on how hard it is to find a statistically significant result when assessing student change on a student‐by‐student basis. This article discusses valid methods for testing the significance of gain scores of individual students.
The effect of dental bleaching on pulpal tissue response in a diabetic animal model
Authors: Cintra L. T. A. , Ferreira L. L. , Benetti F. , Gastélum A. A. , Gomes‐Filho J. E. , Ervolino E. , Briso A. L. F.
Published: September 2016

Aim

To evaluate pulpal tissue response after dental bleaching in normal and alloxan‐induced diabetic rats.

Methodology

Twenty‐eight rats were divided into two groups of normoglycaemic and diabetic rats (n = 14). Diabetes mellitus (DM) was induced with alloxan. After DM confirmation, all rats were anaesthetized and dental bleaching was performed with 35% hydrogen peroxide (H2O2) on the right maxillary molars for 30 min. Left molars were used as controls. Bleaching resulted in four hemimaxillae groups: normoglycaemic (N), N‐bleached (NBle), diabetic (D) and D‐bleached (DBle). After 2 or 30 days, the animals were euthanized and the hemimaxillae were removed, processed for histopathological analysis and stained with haematoxylin–eosin (HE), Masson's trichrome (MT) and picrosirius red (PSR). Results obtained within animals (normoglycaemic or diabetic rats) were submitted to Wilcoxon or paired t‐tests, and between animal (normoglycaemic and diabetic rats), to Mann–Whitney test or t‐tests.

Results

At 2 days, the NBle group had a mild inflammatory infiltration in the pulpal tissue, whilst the DBle had severe inflammation or necrosis (P < 0.05). At 30 days, no inflammation was present. However, a significant difference in pulp chamber area reduction by reactionary dentine deposition was found between the NBle and DBle groups (P < 0.05). At 2 days, fewer immature collagen fibres and more mature collagen fibres were noted in the NBle, D and DBle groups; this was significantly different when compared to the N group (P < 0.05). At 30 days, significantly fewer immature collagen fibres and more mature collagen fibres were noted in NBle compared with DBle group (P < 0.05).

Conclusions

The inflammatory tissue response in rats’ teeth after dental bleaching was greater in diabetic rats. Additionally, the increase in reactionary dentine deposition and mature collagen fibres observed in diabetic rats needs further evaluation to confirm the present results.
The Essence of Dynamic Capabilities and their Measurement
Authors: Laaksonen Ola , Peltoniemi Mirva
Published: September 2016

The growing popularity of explaining firm performance through dynamic capabilities has motivated plenty of conceptual development in the field. However, empirical approaches to measuring dynamic capabilities have so far not been under comprehensive scrutiny. The authors; purpose is to assess the extent to which different ways of measuring dynamic capabilities in quantitative studies correspond to the theoretical essence of the concept, and develop recommendations for future research. They find that four types of operationalizations have been used: (1) managers’ evaluations; (2) financial data; (3) company's experience, actions and performance; and (4) managers’ or employees’ experience, actions and performance. Based on their analysis, the authors provide eight recommendations for future research that relate to identifying ordinary and dynamic capabilities, avoiding common method bias, taking into account the quality and fitness rather than the quantity of dynamic capabilities, and acknowledging the cumulativeness of dynamic capabilities through the use of longitudinal data. They conclude that refining the dynamic capability operationalizations would help to formulate competing hypotheses and to increase the theoretical precision of the field.
Providing prostate cancer survivorship care in Japan: Implications from the USA care model
Authors: Osawa Takahiro , Wittmann Daniela , Jimbo Masahito , Keller Evan T , Namiki Shunichi , Abe Takashige , Shinohara Nobuo , Skolarus Ted A
Published: September 2016

Despite an increasing number of prostate cancer survivors in Japan, the current delivery of prostate cancer survivorship care is insufficient and lacks a multidisciplinary approach. We carried out a study to characterize prostate cancer survivorship care in Japan, examine the Japanese workforce available to deliver survivorship care, introduce a conceptual framework for survivorship and identify opportunities to improve Japanese survivorship care. We systematically searched PubMed for prostate cancer survivorship care studies, including those from Japan. We also searched the internet for prostate cancer guidelines relevant to survivorship care. We found 392 articles, of which 71 were relevant, read in detail and reported here. In Japan, survivorship care is mostly provided by urologists. Primary care as a specialty does not exist in Japan, and there are no independent nurse practitioners or physician assistants to assist with survivorship care. Japanese quality of life studies characterize the long‐term effects of prostate cancer treatment, but routine use of patient‐reported outcomes is not common in Japan. In the USA, in light of a growing comprehensive awareness of challenges facing survivors and their providers, the American Cancer Society prostate cancer survivorship care guidelines serve as a tool for optimizing the management of long‐term treatment effects and coordination of care. In order to deliver high‐quality survivorship care in Japan, urologists need to establish collaborations with other disciplines within the delivery system. A multidisciplinary guideline for prostate cancer survivorship care in Japan appears warranted.
Three‐dimensional fate mapping of larval tissues through metamorphosis in the glass sponge Oopsacas minuta
Authors: Leys Sally P. , Kamarul Zaman Afyqah , Boury‐Esnault Nicole
Published: September 2016

The tissue of glass sponges (Class Hexactinellida) is unique among metazoans in being largely syncytial, a state that arises during early embryogenesis when blastomeres fuse. In addition, hexactinellids are one of only two poriferan groups that already have clearly formed flagellated chambers as larvae. The fate of the larval chambers and of other tissues during metamorphosis is unknown. One species of hexactinellid, Oopsacas minuta, is found in submarine caves in the Mediterranean and is reproductive year round, which facilitates developmental studies; however, describing metamorphosis has been a challenge because the syncytial nature of the tissue makes it difficult to trace the fates using conventional cell tracking markers. We used three‐dimensional models to map the fate of larval tissues of O. minuta through metamorphosis and provide the first detailed account of larval tissue reorganization at metamorphosis of a glass sponge larva. Larvae settle on their anterior swimming pole or on one side. The multiciliated cells that formed a belt around the larva are discarded during the first stage of metamorphosis. We found that larval flagellated chambers are retained throughout metamorphosis and become the kernels of the first pumping chambers of the juvenile sponge. As larvae of O. minuta settle, larval chambers are enlarged by syncytial tissues containing yolk inclusions. Lipid inclusions at the basal attachment site gradually became smaller during the six weeks of our study. In O. minuta, the flagellated chambers that differentiate in the larva become the post‐metamorphic flagellated chambers, which corroborate the view that internalization of these chambers during embryogenesis is a process that resembles gastrulation processes in other animals.
Atopic and vernal keratoconjunctivitis: differences and similarities
Authors: Bremond‐Gignac D.
Published: September 2016

Vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC) represents two severe forms of ocular allergies. In children both are rare diseases and may lead to visual impairment. VKC is a disease that affects primarily boys and children from 3 to 16 years old. Usually VKC disappears at adolescence. Photophobia and tearing are highly specific symptoms other than those usually observed in common ocular allergy as itching and grittiness. Two forms of the disease occur tarsal and limbal vernal keratoconjunctivitis. Tarsal form is marked by cobblestone papillae on the superior tarsal conjunctiva. Limbal form is marked by a broad thickened, circumferential gelatinous opacification of the limbus. Horner‐Trantas dots are characteristic of this form. AKC in children can be misdiagnosed as the presentation appears similar however atopic dermatitis is accompanying the ocular allergy with skin dryness signs. The specific signs of each disease will be detailed. The diagnosis has to be performed as early as possible in order to specify the prognosis, regression in VKC, progression in AKC.
Controversies between how to handle uveitis and glaucoma. The point of view of the glaucoma specialist
Authors: Bron A.
Published: September 2016

Raised intraocular pressure and glaucoma are frequently seen in uveitis, and may represent a serious complication. Inflammatory substances released during uveitis and the treatments used, mainly corticosteroids, probably alter the normal anatomic structure of the anterior chamber and angle, influencing aqueous dynamics.

The clinical presentations may vary according to the irido‐corneal angle. In angle closure, iris bombé is well recognised due to the acute elevation of IOP. However when the angle remains open, a careful monitoring of IOP and optic nerve head are needed, because the evolution is more insidious. Therefore gonioscopy is the key examination in the diagnosis and management of secondary IOP elevations and glaucomas and allows an appropriate treatment.
High‐intensity focused ultrasound treatment for open angle glaucoma
Authors: Aptel F.
Published: September 2016

Many physical methods have been proposed to destroy the ciliary body, resulting in coagulation necrosis following heating (laser) or freezing (cryotherapy). These methods have two major drawbacks: they are nonselective for the target tissue and have an unpredictable dose–effect relationship. To overcome these drawbacks and take advantage of recent breakthroughs in the field of high‐intensity focused ultrasound (HIFU) technology, a new device was developed to achieve a selective coagulation of the ciliary body while sparing the adjacent structures. This device is a ring‐shaped probe with six miniaturized HIFU transducers. Experimental studies have shown a selective coagulation of the treated ciliary processes. Four clinical studies have been conducted. The first one was a pilot study designed to evaluate the safety in a small number of eyes with refractory and advanced glaucoma. The two other studies were multicenter studies designed to evaluate the efficacy and safety in eyes with open‐angle glaucoma and less advanced disease, but still refractory to filtering surgery. Since these studies have demonstrated a nice tolerability, a fourth study was conducted in patients with early glaucoma naïve of any previous filtering surgery.
Retinal vasculitis
Authors: Abu El Asrar A.
Published: September 2016

Retinal vaculitis is a sight‐threatening inflammatory eye condition that involves the retinal vessels. Detection of retinal vasculitis is made clinically, and is confirmed with the help of fundus fluorescein angiography. Active vascular disease is characterized by exudates around retinal vessels resulting in white sheathing or cuffing of the affected vessels. In this review, a practical approach to the diagnosis of retinal vasculitis is discussed based on ophthalmoscopic and fundus fluorescein angiographic findings.
The indications
Authors: Smith R.
Published: September 2016

(i) What signs and symptoms prompt test request? (ii) Which test do I request? (iii) What information should I give on the referral letter?

Visual electrophysiology tests are often requested as part of a clinical work‐up of patients with suspected retinal or optic nerve disease, or unexplained visual symptoms. Occasionally, tests will provide an immediate and unequivocal diagnosis, but more often, the results of tests must be interpreted in the context of the patient's clinical history, examination findings and the results of other investigations. This talk will show how requesting clinicians and the electrophysiology lab can work together to obtain the maximum clinical value from visual electrophysiology tests.
Retinal tests
Authors: Robson A.
Published: September 2016

Visual symptoms are often non‐specific and fundus signs such as disc pallor can result from retinopathy or optic neuropathy. Retinal and macular pathologies may not be evident on clinical examination and visual electrophysiology provides an objective method of localising dysfunction along the visual pathway. This presentation will focus on the assessment of macular function using pattern and multifocal electroretinography (PERG; MfERG) and on the characterisation of retinal function using full‐field electroretinography (ERG). The comparison of PERG or MfERG with ERG allows differentiation between macular and generalised retinal dysfunction. Pattern ERG may also be used to assess retinal ganglion cell function and complements cortical visual evoked potential (VEP) assessment of optic nerve and post‐retinal function. Objective assessment of macular function (PERG/MfERG) is usually essential to exclude a macular cause of VEP abnormality and normal retinal electrophysiology may prompt the need for additional VEP testing or neuroradiology. The use of these techniques will be highlighted using illustrative cases.
Controversies in the use of steroids
Authors: Kugelberg M.
Published: September 2016

Cataract surgery is globally one of the most common surgical procedures carried out today. Postoperatively, inflammation in the anterior chamber is nearly inevitable. In order to reduce the inflammatory reaction, patients are commonly prescribed corticosteroid or/and NSAID eye drops 3–4 weeks following surgery. However, compliance is often poor among these elderly patients. Different ways to tackle the problem has been explored. One way is to coat the intraocular lens with steroids. Another way is to inject a substance perioperatively, either as an intracameral injection, subconjunctival injection, or to inject a little dissolvable implant containing steroids. With steroids, there is always the problem with intraocular pressure rise in some patients, making the task more difficult. An overview of the field will be presented, as well as research results.

It is an important topic since cataract surgery is one of the most common surgical interventions in the world. If we can find a substance and formula that can easily be injected at the end of surgery, and replace the treatment with eye drops, it would be of importance. Postoperative complications such as corneal edema, macular edema and posterior adhesions would also be reduced.
Overview of the epidemiology and pathology of conjunctival tumours
Authors: Loeffler K.U.
Published: September 2016

Conjunctival lesions comprise a variety of benign, pre‐malignant, and malignant tumours. While epidemiologic statistics are difficult and vary between populations, a correct diagnosis is pivotal for appropriate management. This presentation aims to demonstrate the most important conjunctival tumours and their histopathology thereby allowing for a better understanding of clinical features and the respective therapeutic intervention.
Retinal glial cells
Authors: Osborne N.
Published: September 2016

The retina is populated by, in addition to neurons, three types of glial cell: Müller cells, astrocytes, and microglia. All cell‐types within the retina communicate with each other as well as being closely associated with the retinal vasculature. Müller cells are uniquely present in vertebrate retinas principally supporting neuronal functions (by increasing the signal‐to‐noise ratio of information processing) and survival (by maintaining a metabolic ‘symbiosis’ with the neurons) in different ways. They also have the ability to uniquely guide light towards the photoreceptors and are capable of ‘sensing’ neuronal activity as well as responding to physiological light stimulation by adjacent photoreceptors with two distinct types of intracellular calcium rises. It is now clear that retinal glia contribute significantly to the structural and functional integrity of the retina but also play important roles in various retinopathies that include age‐related macular degeneration, retinitis pigmentosa, retinal degeneration, glaucoma, and diabetic retinopathy. It is anticipated that as we gather an even deeper understanding of retinal glia function and dysfunction unique therapies will evolve to treat specific retinal pathologies.
Identifying VEGF‐independent factors for targeted antiangiogenic therapy in the cornea
Authors: Lagali N. , Mukwaya A. , Mirabelli P. , Jensen L. , Xeroudaki M. , Ali Z. , Peebo B.
Published: September 2016

Purpose

To identify prospective inhibitors of inflammatory angiogenesis that operate largely independent of the VEGF pathway.

Methods

Inflammatory angiogenesis was induced in the murine cornea using surgical sutures. Thereafter separate experiments were conducted to (i) prevent neovascularization in an early phase by steroid (dexamethasone) or anti‐VEGFA therapy, and (ii) regress existing neovessels by removal of the initial stimulus. Phenotypic changes were examined by in vivo corneal imaging, whole‐transcriptome expression analysis was performed by comparative bioinformatics analysis of gene microarray data, and expression of target genes of interest was confirmed by RT‐PCR.

Results

Steroid treatment halted initial angiogenic sprouting while anti‐VEGF therapy was less effective. Steroids targeted key inflammatory and angiogenic pathways largely unaffected by anti‐VEGF treatment. Interestingly, several key inflammatory and angiogenic pathways unrelated to VEGF were suppressed during natural angiogenic regression while endogenous inhibitors of angiogenesis were activated.

Conclusion

The identified factors may represent novel therapeutic targets for possible mono‐ or combination therapy with anti‐VEGF agents to improve efficacy.
B27‐associated uveitis, Fuchs uveitis
Authors: Willermain F.
Published: September 2016

B27‐associated uveitis is a very frequent form of non infectious intraocular inflammation which account for approximately 50% of acute anterior uveitis. Its main clinical features, natural history and association with seronegative arthritis are well known. Fuchs uveitis is another frequent cause of anterior and intermediate uveitis. Its natural history is well characterised as well as its association with intraocular production of anti‐rubella antibodies. Both diseases are thus often considered as easy diagnosis. However, several aspects of those diseases remain challenging and debated. In this interactive course, based on clinical cases, we will insist on those difficult aspects as well as on the more recent issues discussed in the literature.
Is the increasing exposure of the eye to near‐infrared radiation from remote controls and sensing a threat to the lens?
Authors: Yu Z. , Schulmeister K. , Talebizadeh N. , Kronschläger M. , Söderberg P.
Published: September 2016

The current safety guideline for near infrared radiation (IRR) exposure in the crystalline lens is based on thermal damage. However, two previous findings implied that there may be a cumulative photochemical effect. The present study aims to investigate if near IRR induces cumulative lens damage considering irradiance exposure time reciprocity. Before exposure, 6‐weeks‐old albino rats were anesthetized and the pupils of both eyes were dilated. Five minutes after pupil dilation, the animals were unilaterally exposed to 1,090 nm IRR within the pupil area. Temperature was recorded with thermocouples placed in the selected positions of the eye. At the planned post‐exposure time, the animal was sacrificed and the lenses were extracted for measurements of forward light scattering and macroscopic imaging. The findings that an in vivo 8 sec exposure to near IRR at 1090 nm within the pupil resulting in a temperature rise of 10°C at the anterior segment of the rat eye induced cataract with a time delay and no cumulative lens damage occurred after long term exposure to 1,090 nm IRR, indicates that IRR at 1,090 nm produces thermal cataract, probably by indirect heat conduction from absorption in tissues surrounding the lens.
The art of orbital imaging
Authors: Tunc M.
Published: September 2016

The Art of Orbital Imaging in Management of Orbital Tumors:

Orbital imaging is the most important aspect of clinical evaluation in management of challanging cases of orbital tumors. We aim to discuss the key points of imaging studies in clinical evaluation and staging of patients with orbital tumors.

Orbital space is a complex anatomical structure that has close proximity to brain and paranasal sinuses. Various tumours and tumour‐like conditions may arise in orbit, both in adults and children. Orbital imaging is critical for detection, characterization, location, differentiation and treatment planning of these orbital lesions. Interpretation of imaging studies are also prominent for correct clinical staging of certain orbital tumors, such as adenoid cystic carcinoma of the lacrimal gland.

In this section of the course, we will discuss, which imaging techniqe (CT, MRI, MRA, Diifusion weighted imaging etc) should be preferred in differential diagnosis, treatment planning and follow up of orbital tumors to achieve the most useful information. Furthermore, the imaging characteristics of common orbital tumors will be emphasized and discussed in depth in the context of this course.
OPA1 gene and mitochondrial optic neuropathy: disease mechanisms and potential therapies
Authors: Votruba M.
Published: September 2016

Primary inherited optic neuropathies are a group of blinding genetic disorders in which optic atrophy secondary to loss of retinal ganglion cells is a key clinical feature. The commonest causes world‐wide are mutation in mitochondrial DNA (causing Leber's Hereditary Optic Neuropathy) and mutation in the nuclear gene, OPA1 (causing Autosomal Dominant Optic Atrophy: ADOA). 60–75% of patients with autosomal dominant optic atrophy have mutations in the OPA1 gene. The OPA1 protein is targeted to the mitochondria and is involved in regulation of mitochondrial fusion. A better understanding of mitochondrial function, including dynamics, is revealing that functional and structural changes in mitochondrial morphology are important factors in diseases of ageing in the eye and visual system. Key proteins have been discovered which control the balance of mitochondrial fusion and fission and have a range of other functions, such as controlling maintenance of mitochondrial DNA, cell death, autophagy, mitochondrial metabolism and redox signalling. A decline in mitochondrial function plays a role in the ageing process and increases the incidence of age‐related disorders. Mitochondrial optic neuropathies are ‘orphan’ diseases but with the advent of recent trials of novel therapies in patients with the mitochondrial optic neuropathy, Leber's hereditary optic neuropathy, there is the first glimmer of hope for the treatment of this group of patients.
Perturbed mitochondrial homeostasis in LHON: a new target for rescue strategy
Authors: Carelli V.
Published: September 2016

Leber's hereditary optic neuropathy (LHON) is the most frequent mitochondrial disease due to mitochondrial DNA mutations affecting complex I. The pathogenic mechanism includes complex I deficiency leading to reduced ATP synthesis, increased reactive oxygen species production and lowered threshold for apoptosis. Cell compensatory mechanisms include activation of mitochondrial biogenesis, but also increased removal of damaged mitochondria by mitophagy. The balance between ‘mito‐bioegenesis’ and ‘mito‐phagy’ is key to mitochondrial homeostasis and efficient compensation, driving incomplete disease penetrance. These mechanisms reflect on the function of retinal ganglion cells (RGCs), the disease cell target, where increased mitochondrial organelles need to be transported along the axons. Ultimately, axonal traffic jam of mitochondria may result in a catastrophic series of events leading to RGCs degeneration. The master regulation impinging on mito‐biogenesis and mito‐phagy is a crucial crossroad for sensing mitochondrial dysfunction and is the target for therapeutic approaches aimed at modulating mito‐biogenesis and mito‐phagy, inhibiting apoptosis, and correcting or bypassing complex I dysfunction.
The initial consultation
Authors: Spileers W.
Published: September 2016

Purpose

Patients with complaints of seeing badly in the dark need a full ophthalmological workup.

Methods

Acquired versus congenital nightblindness has to be questioned in a full anamnesis. Visual acuity, biomicroscopy and fundus examination are essential followed by visual field testing and possibly visual electrophysiology (flash ERG).

Results

Several causes of congenital and acquired nightblindness can be found. Not all patients complaining of seeing badly in the dark are ‘nightblind’.

Conclusion

A full clinical ophthalmological work up can identify adequately several causes of night blindness.
What did we learn from this session?
Authors: Abegao Pinto L.
Published: September 2016

An overall discussion of the subject will be held. The audience and speakers will both be encouraged to discuss the pros and cons of each of the previous lectures as well as to briefly brainstorm on the problems facing the design of an ideal glaucoma rotation.
How to tackle these difficult cases
Authors: Abegao Pinto L.
Published: September 2016

Recent technological advances have led to an increase in the number of options when choosing a glaucoma surgery. However, the boundaries of each technique have not yet been defined. Furthermore, profiling patients at risk for complications with these new techniques is still a difficult task as well as identifying the best options on how to solve them. Accordingly, a number of challenging cases will be presented to a panel of glaucoma specialists in order to create an open discussion on which would be the best surgical option and which would be the best strategy to achieve success.