bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic migraine in women is associated with insulin resistance: a cross‐sectional study
Authors: Fava A. , Pirritano D. , Consoli D. , Plastino M. , Casalinuovo F. , Cristofaro S. , Colica C. , Ermio C. , De Bartolo M. , Opipari C. , Lanzo R. , Consoli A. , Bosco D.
Published: November 2013

Background and purpose

Migraine is a common neurological disorder. It can be divided into episodic migraine (EM) and chronic migraine (CM), based on headache frequency. Some studies have shown that insulin sensitivity is impaired in migraine; moreover, hypertension, diabetes and obesity are common in patients with CM. The aim of this study was to assess serum glucose, insulin levels and insulin resistance (IR) in a sample of episodic migraineurs, chronic migraineurs and non‐pain healthy controls.

Methods

Eighty‐three women with EM, 83 with CM and 83 healthy controls were recruited. Headache was diagnosed according to the latest International Classification of Headache Disorders 2 criteria. Waist circumference, body mass index (BMI) and blood pressure were measured. Checked metabolic parameters included fasting glucose, the 2 h 75 g oral glucose tolerance test (2 h OGTT), serum HbA1c, blood lipid profile, C‐reactive protein and prolactin. The homeostasis model assessment formula was used to calculate IR.

Results

A significant prevalence of IR in CM was observed (P = 0.002). No significant associations were found with fasting glycaemia, the 2 h OGTT, HbA1c, blood lipid profile, C‐reactive protein, prolactin and waist circumference. Obesity (BMI >30 kg/m2) was associated with an increased risk of CM [odds ratio (OR) 2.4]. When the outcome of interest was the association between IR and obesity, the OR was significantly increased compared with IR alone (OR = 13.2).

Conclusion

This may suggest that CM is associated with IR status, particularly when it is in partnership with obesity.
Head trauma sustained under the influence of alcohol is a predictor for future traumatic brain injury: a long‐term follow‐up study
Authors: Vaaramo K. , Puljula J. , Tetri S. , Juvela S. , Hillbom M.
Published: November 2013

Background and purpose

Hazardous drinking may result in recurrent head trauma. It was investigated whether head trauma sustained under the influence of alcohol is a predictor of future traumatic brain injury (TBI).

Methods

All subjects with head trauma (n = 827) brought to the emergency room at Oulu University Hospital during 1999 were identified and followed up until death or the end of 2009. The National Hospital Discharge Register and hospital charts were used to identify TBIs during the follow‐up and Kaplan–Meier curves and the Cox proportional hazards model were used to characterize predictors of TBI.

Results

During the total follow‐up of 7386 person‐years, 52/827 subjects sustained a new head trauma with TBI and the risk of TBI was significantly (P = 0.005) higher amongst subjects who had been under the influence of alcohol at the time of the index trauma in 1999. New TBI occurred under the influence of alcohol in 30/52 cases (57.7%). An alcohol‐related index trauma [adjusted hazard ratio (HR) 2.51, 95% confidence interval (CI) 1.38–4.56, P < 0.01] and history of TBI (HR 3.39, 95% CI 1.32–8.72, P < 0.05) were independent risk factors for subsequent TBI after adjustment for sex and age. A history of harmful drinking was also a significant risk factor (adjusted HR 10.37, 95% CI 5.53–19.43, P < 0.001). In the subset of 396 patients having an index head trauma without TBI, this being alcohol related was also a significant risk factor for subsequent TBI after adjustment for sex, age and history of TBI (HR 3.54, 95% CI 1.36–9.18, P = 0.009).

Conclusions

Even head trauma without TBI under the influence of alcohol implies an elevated risk of subsequent TBI. A brief intervention to reduce hazardous drinking is needed to prevent TBI.
3TMRIimproves the detection of transmantle sign in type 2 focal cortical dysplasia
Authors: Mellerio Charles , Labeyrie Marc‐Antoine , Chassoux Francine , Roca Pauline , Alami Odile , Plat Monique , Naggara Olivier , Devaux Bertrand , Meder Jean‐François , Oppenheim Catherine
Published: November 2013

Purpose

Type 2 focal cortical dysplasia (FCD2) is one of the main causes of refractory partial epilepsy, but often remains overlooked byMRI. This study aimed to elucidate whether 3TMRIoffers better detection and characterization ofFCD2 than 1.5T, using similar coils and acquisition time.

Methods

Two independent readers reviewed the 1.5T and 3TMRimages of 25 patients with histologically provenFCD2. For both magnetic fields, the ability to detect a lesion was analyzed. We compared the identification of each of the five criteria typical ofFCD2 (cortical thickening, blurring, cortical signal changes, subcortical signal changes, and “transmantle” sign) and artifacts, using a four‐point scale (0–3). Interobserver reliability for lesion detection was calculated.

Key Findings

Seventeen lesions (68%) were detected at 3T, two of which were overlooked at 1.5T. Interobserver reliability was better at 3T (κ = 1) than at 1.5T (κ = 0.83). The transmantle sign was more clearly identified at 3T than 1.5T (mean visualization score: 1.72 vs. 0.56; p = 0.002).

Significance

The use of 3TMRIin patients suspected of type 2FCDimproves the detection rate and the lesion characterization owing to the transmantle sign being more clearly seen at 3T. This point is of interest, since this feature is considered as anMRsignature ofFCD2.
A new technique for subtotal (cranial wedge) ostectomy in the treatment of impinging/overriding spinous processes: Description of technique and outcome of 25 cases
Authors: Jacklin B. D. , Minshall G. J. , Wright I. M.
Published: November 2013

Reasons for performing study

Surgical management for overriding spinous processes of the thoracolumbar vertebrae (SPs) is often favoured when conservative therapies have failed, pathology is severe, or in competition horses constrained by drug withdrawal periods.

Objectives

To evaluate whether subtotal (cranial wedge) ostectomy represents an effective treatment for overridingSPs, with short surgery time and low complication rates, maintains the contour of the spine and produces a functionally and cosmetically better outcome than previously reported surgical techniques for management of overriding/impingingSPs.

Study design

Retrospective study.

Methods

A new technique is described and records were retrieved for 25 cases that had undergone the procedure at Newmarket Equine Hospital between 2009 and 2011. Case records were evaluated for anamnesis, clinical findings and details of surgical and post operative management. Outcome of surgery was assessed by telephone questionnaire with owners, relating to both functional and cosmetic results.

Results

Of cases treated using the described technique, 78.9% had resolution of clinical signs and returned to full work and a further 18.2% were improved. Outcome was unrelated to number ofSPs resected or mean radiographic grade of impingement. Cosmetic outcome was described as excellent in 81.8% and good in the remainder. Surgery time ranged from 20 to 70 (median 30) min and there were no intra‐ or post operative complications.

Conclusions

In contrast to previously described amputation techniques, subtotal (cranial wedge) ostectomy removes only impinging portions ofSPs. General anaesthesia and lateral recumbency facilitate access and enable a short surgery time. The procedure maintains the contour of the back and has fewer complications, but produces functional outcomes similar to more invasive procedures.
The effects of acute and chronic exercise on PGC‐1α, irisin and browning of subcutaneous adipose tissue in humans
Authors: Norheim Frode , Langleite Torgrim Mikal , Hjorth Marit , Holen Torgeir , Kielland Anders , Stadheim Hans Kristian , Gulseth Hanne Løvdal , Birkeland Kåre Inge , Jensen Jørgen , Drevon Christian A.
Published: November 2013

Irisin was first identified as a peroxisome proliferator‐activated receptor γ co‐activator‐1α (PGC‐1α) dependent myokine with the potential to induce murine brown‐fat‐like development of white adipose tissue. In humans, the regulatory effect of training on muscle FNDC5mRNA expression and subsequently irisin levels in plasma is more controversial. We recruited 26 inactive men (13 normoglycaemic and normal weight, controls; and 13 slightly hyperglycaemic and overweight, pre‐diabetes group) aged 40–65 years for a 12‐week intervention of combined endurance and strength training with four sessions of training per week. Before and after the 12‐week intervention period, participants were exposed to an acute endurance workload of 45 min at 70% of VO2max, and muscle biopsies were taken prior to and after exercise. Skeletal muscle mRNA for PGC1A and FNDC5 correlated and both PGC1A and FNDC5mRNA levels increased after 12 weeks of training in both control and pre‐diabetes subjects. Circulating irisin was reduced in response to 12 weeks of training, and was increased acutely (~1.2‐fold) just after acute exercise. Plasma concentration of irisin was higher in pre‐diabetes subjects compared with controls. There was little effect of 12 weeks of training on selected browning genes in subcutaneous adipose tissue. UCP1mRNA did not correlate with FNDC5 expression in subcutaneous adipose tissue or skeletal muscle or with irisin levels in plasma. We observed no enhancing effect of long‐term training on circulating irisin levels, and little or no effect of training on browning of subcutaneous white adipose tissue in humans.
Syntactic gains in short‐term study abroad
Authors: Arnett Carlee
Published: November 2013

This article reports the results of a study of the syntactic acquisition of nine participants in a short‐term study abroad program that was designed to complete the second year of German. Data compared study abroad students' use of accusative and dative case prepositions and ditransitives, auxiliary selection in the past tense, and dative verbs with the use of those constructions by students who completed the second‐year course sequence at the home institution. The study abroad students performed at about the same level as the on‐campus students on all syntactic measures but produced many more ditransitive clauses.
Forecasting GDP at the Regional Level with Many Predictors
Authors: Lehmann Robert , Wohlrabe Klaus
Published: November 2013

In this study, we assess the accuracy of macroeconomic forecasts at the regional level using a large data set at quarterly frequency. We forecast gross domestic product (GDP) for two German states (Free State of Saxony and Baden-Württemberg) and Eastern Germany. We overcome the problem of a ‘data-poor environment’ at the sub-national level by complementing various regional indicators with more than 200 national and international indicators. We calculate single-indicator, multi-indicator, pooled and factor forecasts in a ‘pseudo-real-time’ setting. Our results show that we can significantly increase forecast accuracy compared with an autoregressive benchmark model, both for short- and long-term predictions. Furthermore, regional indicators play a crucial role for forecasting regional GDP.
Does Democratization Foster State Consolidation? Democratic Rule, Political Order, and Administrative Capacity
Authors: Carbone Giovanni , Memoli Vincenzo
Published: November 2013

The established view in political science is that a sound and functioning state has to be in place before democracy can be introduced. State first, and then democracy. While acknowledging the existence of a basic state infrastructure as a necessary starting point, we examine the possibility that democratization itself may play an important role in the subsequent development and consolidation of the state. We do this by addressing the major conceptual and methodological shortcomings of existing research on this topic. The results of our panel analysis, covering a population of 122 countries, show that both a country's level of democracy and the interaction between degree and duration of democracy positively and significantly affect the consolidation of the state and of its two key individual dimensions, namely, political order and administrative capacity.
Online strategies to facilitate health‐related knowledge transfer: a systematic search and review
Authors: Mairs Katie , McNeil Heather , McLeod Jordache , Prorok Jeanette C. , Stolee Paul
Published: November 2013

Background

Health interventions and practices often lag behind the available research, and the need for timely translation of new health knowledge into practice is becoming increasingly important.

Objective

The objective of this study was to conduct a systematic search and review of the literature on online knowledge translation techniques that foster the interaction between various stakeholders and assist in the sharing of ideas and knowledge within the health field.

Methods

The search strategy included all published literature in the English language since January 2003 and used the medline, Cumulative Index to Nursing and Allied Health Literature (cinahl), embase and Inspec databases.

Results

The results of the review indicate that online strategies are diverse, yet all are applicable in facilitating online health‐related knowledge translation. The method of knowledge sharing ranged from use of wikis, discussion forums, blogs, and social media to data/knowledge management tools, virtual communities of practice and conferencing technology – all of which can encourage online health communication and knowledge translation.

Conclusions

Online technologies are a key facilitator of health‐related knowledge translation. This review of online strategies to facilitate health‐related knowledge translation can inform the development and improvement of future strategies to expedite the translation of research to practice.
Effect of muscle, ageing time and modified atmosphere packaging conditions on the colour, oxidative and microbiological stability of packed beef
Authors: Owczarek‐Fendor Agnieszka , Vermeulen An , Van Bree Ilse , Eriksson Markus , Lescouhier Stefaan , De Smet Stefaan , De Meulenaer Bruno , Devlieghere Frank
Published: November 2013

The objective of this study was to evaluate the influence of two different vacuum ageing times (7 and 14 days) and the impact of the modified atmosphere packaging (MAP) configuration (gas/product ratios: 0.5 and 1 and gas composition: 70% O2 + 30% CO2 and 40% O2 + 30% CO2 + 30% N2) on the quality of fresh beef during subsequent storage at 4 °C. For this purpose, three separate experiments were performed. For each experiment, two different muscles (Longissimus dorsi and Biceps femoris) were sampled from four double‐muscled Belgian Blue beef carcasses. Next to colour, also the evolution in microbial load, pH, O2 and CO2 in the headspace and lipid oxidation at the meat surface were evaluated. A vacuum ageing for 14 days compared with 7 days resulted in a higher initial microbial load on the day of MAP packaging, which resulted finally in a significantly shorter shelf life. This ageing effect was less pronounced on the colour stability and lipid oxidation of the meat samples. No significant influence of the packaging configuration on any of the analysed parameters (colour, microbial load, pH and lipid oxidation at the meat surface) was observed.
Antibiofilm formation and anti‐adhesive (to HEp‐2 cells) effects of rosemary water extract against some food‐related pathogens
Authors: Elhariry Hesham , Abuzaid Abeer A. , Khiralla Ghada M. , Gherbawy Youssuf
Published: November 2013

The present work aimed to determine the bioactive compounds in two rosemary water extracts (RWE1 and RWE2) and to assess their antimicrobial, anti‐adhesive and antibiofilm potentials against the food‐related Bacillus and Pseudomonas species at concentrations; 4, 8, 12, 16 and 20 mg mL−1. Phenolic compounds and isoflavones in the RWEs were determined using HPLC. The concentrations of most bioactive compounds of RWE1 (benzoic, ellagic, gallic and rosmarinic acids, daidzein and genistein) were higher than that of RWE2. The MIC90 of RWE1 and RWE2 against all tested bacteria was 12 and 16 mg mL−1, respectively. The anti‐adhesive and antibiofilm doses were higher than MIC90. RWE1 and RWE2 showed potential reduction in the bacterial cell adhesion to HEp‐2 cells – 17.5–64.7 and 12.2–52.9%, respectively. In conclusion, this study emphasises the effective use of RWE as a natural anti‐adhesive and antibiofilm agent against Bacillus and Pseudomonas, without difficult extraction procedure.
Effect of xylitol on wheat dough properties and bread characteristics
Authors: Sun Qingjie , Xing Yan , Xiong Liu
Published: November 2013

The aim of the experiment was to evaluate the effect of xylitol on wheat dough properties and bread qualities. The results showed that peak viscosity of bread flour containing 20% xylitol was about 12.59% higher than that of the control. The development time and stability time of dough containing 5% xylitol were 2.55 and 1.62 min longer than those of the control, and the drop value decreased from 454 FU to 359 FU. The extensibility of dough containing 10% xylitol was 21 mm longer than that of the control. The maximum resistance and energy area showed an increasing trend. Scanning electron microscopy images showed a discontinuous gluten matrix in which starch granules were not covered completely with gluten when containing xylitol. The springiness of bread with 10% xylitol was increased by 10.6% compared with that of the control, while the hardness was decreased by 21.5%. The bread added 10% and 15% xylitol had higher scores than the control.
The meaning of life and health experience for the Chinese elderly with chronic illness: A qualitative study from positive health philosophy
Authors: Zhang Heng , Shan WeiYing , Jiang AnLi
Published: November 2013

Ageing and the concurrent prevalence of chronic disease in older adults produce a great burden and challenge for family, society and individuals. There is a definite need to build the science about caring for older Chinese adults from their perspective to inform health‐care professionals. The aim of the study was to investigate the meaning of life and health experience of Chinese elderly with chronic illness and identify health potential from a positive perspective. A qualitative descriptive study was undertaken to interview 11 older adults ages 64–92 in a day centre. In 2011, the data were collected and analysed by thematic analysis. Four interrelated themes indicated a rich meaning of life and health experience from the older adults: (i) happiness lies in contentment; (ii) sense of responsibility; (iii) letting nature take its course; (iv) and proactive self‐balance. These interrelated themes with partial conflict presented a dialectic meaning of life and were interpreted from traditional Chinese culture and compared with positive health philosophy. The significance of finding will encourage nursing practice work with clients and identify the potential and self‐help strength of the elderly.
Testing the psychometric properties of the Brisbane Practice Environment Measure using Exploratory Factor Analysis and Confirmatory Factor Analysis in an Australian registered nurse population
Authors: Reid Carol , Courtney Mary , Anderson Debra , Hurst Cameron
Published: November 2013

A cross‐sectional survey was conducted, and the construct validity and reliability of the Brisbane Practice Environment Measure in an Australian sample of registered nurses were examined. Nurses were randomly selected from the database of an Australian nursing organization. The original 33 items of the Brisbane Practice Environment Measure were utilized to inform the psychometric properties using confirmatory factor analysis. The Cronbach's alpha was 0.938 for the total scale and ranged 0.657–0.887 for the subscales. A five‐factor structure of the measure was confirmed, χ2 = 944.622, (P < 0.01), χ2/d.f. ratio = 2.845, Tucker Lewis Index 0.929, Root Mean Square Error = 0.061 and Comparative Fit Index = 0.906. The selected 28 items of the measure proved reliable and valid in measuring effects of the practice environment upon Australian nurses. The implications are that regular measurement of the practice environment using these 28 items might assist in the development of strategies which might improve job satisfaction and retention of registered nurses in Australia.
Establishment of transgenic silkworms expressing GAL4 specifically in the haemocyte oenocytoid cells
Authors: Tsubota T. , Uchino K. , Kamimura M. , Ishikawa M. , Hamamoto H. , Sekimizu K. , Sezutsu H.
Published: November 2013

Insect haemocytes play significant roles in innate immunity. The silkworm, a lepidopteran species, is often selected as the model for studies into the functions of haemocytes in immunity; however, our understanding of the role of haemocytes remains limited because the lack of haemocyte promoters for transgene expression makes genetic manipulations difficult. In the present study, we aimed to establish transgenic silkworm strains expressing GAL4 in their haemocytes. First, we identified three genes with strong expression in haemocytes, namely, lp44, Haemocyte Protease 1 (HP1) and hemocytin. Transgenic silkworms expressing GAL4 under the control of the putative promoters of these genes were then established and expression was examined. Although GAL4 expression was not detected in haemocytes of HP1‐GAL4 or hemocytin‐GAL4 strains, lp44‐GAL4 exhibited a high level of GAL4 expression, particularly in oenocytoids. GAL4 expression was also detected in the midgut but in no other tissues, indicating that GAL4 expression in this strain is mostly oenocytoid‐specific. Thus, we have identified a promoter that enables oenocytoid expression of genes of interest. Additionally, the lp44‐GAL4 strain could also be used for other types of research, such as the functional analysis of genes in oenocytoids, which would facilitate advances in our understanding of insect immunity.
Impact of the 2009 Melbourne heatwave on a major public hospital
Authors: Lindstrom S. J. , Nagalingam V. , Newnham H. H.
Published: November 2013

In the week following the onset of the 2009 heatwave in Melbourne, Australia, The Alfred Hospital observed a significant increase in total hospital admissions (adjusted incidence rate ratio (IRR) 1.11, P = 0.046), emergency department presentations (IRR 1.15, P < 0.01) and general medical admissions (IRR 1.81, P < 0.01). Under the general medical unit there was a rise in the number of deaths (IRR 3.9, P < 0.01), and patients with a broad range of disorders, particularly of the endocrine/metabolic (IRR 2.2, P < 0.01), circulatory (IRR 1.9, P < 0.01) and genitourinary (IRR 2.6, P < 0.01) systems.
No evidence for zoonotic transmission of H3N8 canine influenza virus among US adults occupationally exposed to dogs
Authors: Krueger Whitney S. , Heil Gary L. , Yoon Kyoung‐Jin , Gray Gregory C.
Published: November 2013

Objectives

The zoonotic potential of H3N8 canine influenza virus (CIV) has not been previously examined; yet considering the popularity of dogs as a companion animal and the zoonotic capabilities of other influenza viruses, the public health implications are great. This study aimed to determine the seroprevalence of antibodies against CIV among a US cohort.

Design

A cross‐sectional seroepidemiological study was conducted between 2007 and 2010.

Setting

Recruitments primarily occurred in Iowa and Florida. Participants were enrolled at dog shows, or at their home or place of employment.

Sample

Three hundred and four adults occupationally exposed to dogs and 101 non‐canine‐exposed participants completed a questionnaire and provided a blood sample.

Main outcome measures

Microneutralization and neuraminidase inhibition assays were performed to detect human sera antibodies against A/Canine/Iowa/13628/2005(H3N8). An enzyme‐linked lectin assay (ELLA) was adapted to detect antibodies against a recombinant N8 neuraminidase protein from A/Equine/Pennsylvania/1/2007(H3N8).

Results

For all assays, no significant difference in detectable antibodies was observed when comparing the canine‐exposed subjects to the non‐canine‐exposed subjects.

Conclusion

While these results do not provide evidence for cross‐species CIV transmission, influenza is predictably unpredictable. People frequently exposed to ill dogs should continually be monitored for novel zoonotic CIV infections.
On the Role of Cultural Distance in the Decision to Cross‐List
Authors: Dodd Olga , Frijns Bart , Gilbert Aaron
Published: November 2013

This paper examines the role of culture in the choice of the destination market for cross‐listing firms. We argue that firms cross‐list in markets with greater cultural similarities, because 1) investors are more willing to invest in culturally familiar firms and 2) managers seek to avoid potential conflicts with culturally disparate investors and managers. Employing Hofstede's cultural dimensions, we find that firms from developed countries display greater cross‐listing propensity towards culturally similar countries. These results are robust to various alternative cultural measures. We further find that it is mainly the difference in uncertainty avoidance and individualism that affect cross‐listing decisions.
On non‐bossy matching rules in two‐sided matching problems
Authors: Kongo Takumi
Published: November 2013

It is well known that in two‐sided matching problems, stability is incompatible with non‐bossiness. We extensively study whether there exists a non‐bossy matching rule that satisfies certain properties weaker than stability. Results demonstrate that weak stability and respect for recursive unanimity are incompatible with non‐bossiness; however, paired individual rationality and efficiency, and respect for 2‐unanimity, are compatible with non‐bossiness. Thus, a clear contrast exists between strategy‐proofness, which is incompatible with all three aforementioned properties and the paired properties, and non‐bossiness, which is incompatible with only two of them.
A necessary and sufficient single‐profile condition for transitivity of the Pareto extension order
Authors: Xefteris Dimitrios
Published: November 2013

This note identifies a necessary and sufficient single‐profile condition for transitivity of the Pareto extension order when individuals are never indifferent between two distinct alternatives. We find that the Pareto extension order is transitive if and only if for any triplet of the available alternatives there exists either a consensus on which is the best, the second best or the worst alternative, or a perfect disagreement on which is the best or the worst alternative.
EVER 2013 Lecture: Advances in OCT imaging
Authors: SCHMETTERER L
Published: November 2013

In the brain there is a tight coupling between local neural activity and local blood flow and metabolism. This phenomenon called neurovascular coupling was proposed more than 100 years ago and since then confirmed by numerous experiments. A breakdown in functional hyperemia has been hypothesized to contribute to loss of neurons in diseases such as stroke, hypertension, spinal‐cord injury and Alzheimer’s disease. In the eye this phenomenon exists as well. During stimulation of the eye with flicker light there is a pronounced increase in retinal and optic nerve head blood flow. The mechanisms underlying neuromuscular coupling in the retina are complex and involve the interaction between neurons, astrocytes and blood vessels. In this process vasoactive arachidonic acid metabolites play a key role. In addition, the vascular endothelium is involved. The response of retinal vessels to flicker stimulation is also modified by nitric oxide and oxygen. Neurovascular coupling is altered in diseases such as glaucoma or diabetes and may contribute to neuronal loss in these diseases. A better understanding of these phenomena is required to achieve neuroprotection via the neuromuscular pathway.
Partial thickness macular holes and pharmacological treatment
Authors: GEORGALAS I
Published: November 2013

Partial thickness macular holes and lamellar macular holes have a different pathophysiological mechanism compare to the full thickness macular holes as well as different management. Surgery is not always an option. This is the case for a group of full thickness macular holes as well, where pharmacological treatment appears to be a very successful option.
Clinical examination of the optic disc? Yes I can!
Authors: JONAS J
Published: November 2013

The course will present and discuss ophthalmoscopic characteristics of the optic nerve head in normal eyes and in glaucomatous eyes, including gamma zone and delta zone of parapapillary atrophy and histologic findings
Imaging in uveitis: techniques and indications
Authors: HERBORT C
Published: November 2013

This tutorial will address the main complementary imaging techniques used in the field of (posterior) uveitis. In case imaging work‐up is decided, fluorescein angiography (FA) is performed routinely since a few decades. FA gives information on the superficial structures and lesions of the fundus including pathology of the retina, retinal vessels, optic disc, and subretinal fluid collection, as well as the RPE for which it is the examination method of choice, and the choriocapillaris in the first seconds of angiography. Most of the time it only confirms and gives the precise extension of lesions already identified by the clinical examination. The choroid is however involved at least as often as the retina and often all or part of choroidal lesions are occult and not detected by the clinical exam or FA. Only indocyanine green angiography (ICGA) gives visual access to choroidal inflammatory pathology where it can distinguish stromal choroidits (birdshot, VKH) from choriocapillaritis (MEWDS, APMPPE, etc). So if angiography is deemed necessary during initial appraisal of a case dual FA/ICGA should be performed as choroiditis can not be excluded "à priori". Other methods addressed will be OCT, UBM, FAF as well as anterior segment OCT.
Glaucoma and the ocular surface
Authors: BRON A
Published: November 2013

Abstract not provided
PF Combo therapy
Authors: SUNARIC MEGEVAND G
Published: November 2013

Abstract not provided
Dietary fat consumption and AMD: Epidemiological facts
Authors: DELCOURT C
Published: November 2013

In 2000, a 50 % lower risk for AMD in regular fish consumers was reported for the first time, in a cross‐sectional analysis of the Blue Mountains Eye Study. Since then, 8 cross‐sectional and case‐control studies have produced similar results, although not always reaching statistical significance. However, cross‐sectional and case‐control studies are subject to reverse causality: subjects with AMD may have decreased their fish consumption because of the disease itself, for instance because of difficulties in shopping and cooking. Six prospective studies, in which dietary habits are assessed before the onset of AMD, have also all shown a reduced risk for AMD in high consumers of fish or omega 3 LC‐PUFA, although not always reaching statistical significance. Finally, use of biomarkers may help overcome many methodological difficulties of dietary assessment (recall bias, imprecisions in assessment of food intake and nutritional content of foods…). In the French Alienor Study, we have recently shown that subjects with high plasma omega3 LC‐PUFA had a lower risk of AMD within the next 10 years. Overall, epidemiological data are strikingly consistent, showing a major reduction of risk for AMD in subjects with high omega3 LC‐PUFA status.

Commercial interest
Challenges in manufacturing an amniotic membrane alternative for corneal regeneration
Authors: WILSON S , HOPKINSON A
Published: November 2013

The current and projected worldwide cornea shortages have acted as a driver for the development of feasible, long‐term alternatives to cadaveric donor tissue. Alternatives in current clinical or pre‐clinical development can be loosely categorised into the following broad areas: keratoprostheses, tissue engineered constructs, xenografts and the use of decellularized/acellular matrices. With respect to corneal regeneration, there are many challenges to address, not least that the corneal structure is unique and difficult to replicate. When manufacturing corneal tissues, the choice of material is a vital consideration as the list of requirements is extensive. They must be biocompatible, (preferably) optically transparent, flexible, and strong, as to withstand manipulation in culture, potential suturing, irrigation and handling during surgery. Furthermore, the manufacturing process needs to be simple with consistent quality, preferably at high speed and low cost. The biodegradability or bioreasorbability of the construct needs consideration to ensure cellular integration, regeneration and reconstruction. Two fundamental objectives concerning corneal regeneration are the maintenance of healthy cell phenotypes either in vitro or in vivo following implantation; and the replication of the native tissue architecture. If both factors are not satisfied, the result is often regenerated tissue mimicking that of scarred native tissue.
Short‐time reproducibility of tearfilm osmolarity measurement assessed with electrical impedance
Authors: SCHMIDL D , KAYA S , NEPP J , SCHMETTERER L , GARHOFER G
Published: November 2013

Purpose There is compelling evidence that increased tearfilm osmolarity is a key pathogenetic mechanism for the development of Dry Eye Syndrom (DES) and its related complications. The current study was performed to assess the short‐time and day‐to‐day reproducibility of an electrical impedance based system for the measurement of tear film osmolarity.

Methods 20 patients with moderate DES and a control group of 20 age and sex matched healthy subjects were included in the study. Tear film osmolarity was measured using a commercially available electrical impedance based “lab on a chip” system (TearLab OcuSens). To measure short‐time reproducibility 3 consecutive measurements were performed. To assess day‐to‐day reproducibility this procedure was repeated on three consecutive study days. Schirmer I test and break up time was performed on each study day. Coefficient of variation (CV) was calculated as a measure of reproducibility.

Results Tear film osmolarity was higher in patients with DES compared to healthy control subjects on all three study days (p<0.05). Short time CV of tearfilm osmolarity on the three study days was 3.18%±2.89%, 2.81%±2.08% and 2.23%±1.85%, respectively. Day‐to‐day variability based on the CV of the three study days was 3.47%±1.69%. As expected, Schirmer I test and BUT was lower in patients with DES compared to healthy subjects on all three study days (p<0.05).

Conclusion Electrical impedance based measurements of tear film osmolarity show good short time and day‐to‐day reproducibility. Whether tear film osmolarity is a suitable clinical parameter to assess severity and to monitor treatment success in patients with DES has yet to be investigated.
Corneal Langerhans cell and dry eye examinations in ankylosing spondylitis
Authors: MARSOVSZKY L , NEMETH J , RESCH MD , TOLDI G , LEGANY N , KOVACS L , BALOG A
Published: November 2013

Purpose To examine the density and the distribution of corneal Langerhans cells (LCs) and to compare the results with dry‐eye related parameters and disease activity in ankylosing spondylitis(AS).

Methods Twenty four AS patients (mean age: 41.8±9.8 years) with various degree of disease activity and twenty four healthy subjects (mean age: 47.9 ± 16.4 years) were enrolled. Ocular surface disease index (OSDI), lid parallel conjunctival folds (LIPCOF), tear break up time (TBUT), and Schirmer test (ST) were evaluated. In addition, central and peripheral LCs numbers and Langerhans cell morphology (LCM) were assessed with in vivo laser confocal microscopy.

Results Tear production was greatly suppressed in patients with more severe systemic inflammation according to the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and C‐reactive protein (CRP) (BASDAI≤4.0 vs BASDAI>4.0 10.2±8.5 vs 4.0±5.3; CRP≤5.0 vs CRP>5.0 17.2±4.2 vs 3.9±5.5 p<0.05 for all). LCs densities and central LCM were greater in AS patients than in the controls (LC density: 77.5±44.9 vs 23.8±33.8 and central LCM: 1.7±0.7 vs 0.95±0.75 p<0.05 for all).

Conclusion Greater corneal LC density and LCM may reflect an increased activation of the corneal innate immune system, which correlates with the systemic activity of AS even without ocular symptoms. Higher systemic inflammation might impair tear production, and it might partly explain the dry eye mechanism.
Importance of taurine in maintaining retinal function
Authors: PICAUD S , FROGER N
Published: November 2013

Taurine depletion has been known to induce photoreceptor degeneration since the 70s. Recently, investigating the retinal toxicity of the antiepileptic drug, vigabatrin, we showed that taurine depletion causes retinal ganglion cell loss. Indeed, the primary site of vigabatrin‐induced injury appears to be located in retinal ganglion cells in patients. The taurine depletion was demonstrated in both vigabatrin‐treated animals and patients. In fact, an increase in intraocular pressure as in glaucoma could also induce a local retinal taurine depletion. Taurine supplementation was neuroprotective in 4 animal models with retinal ganglion cell loss. Taurine acts directly on retinal ganglion increasing their survival in pure cultures. Taurine also reduces their glutamate excitotoxicity in retinal explants. Therefore, taurine is required for the normal maintenance of photoreceptors but also for the maintenance of retinal ganglion cells. Taurine supplementation may therefore provide a novel neuroprotective strategy for retinal diseases like glaucoma.
Possible reasons for a miss match between animal neuroprotection studies and clinical findings
Authors: OSBORNE N
Published: November 2013

A variety of reasons exist to possibly explain why excellent experimental neuroprotection studies have not been translated to a functional attenuation of a defined progressive retinal disease like glaucoma. A major problem exists in judging the validity of published experimental studies. For example, it is questionable how the various animal models used really relate to any specific ocular disease. There is also a tendency to accept studies as being correct when reported in high profile journals and/or from leading groups. Another issue is that methods used for the administration of neuroprotectants that relate to acceptable side effects, penetration, pharmacokinetics and therapeutic efficacy in successful animal studies might not translate in the same way to the human situation. Also, most animal studies do not demonstrate functional neuroprotection but rather the preservation of biochemical, physiological or morphological alterations caused by a defined insult. It should however be pointed out that clinical proof to reproduce experimental studies in relation to ocular neuroprotection remains largely unexplored because of costs and where investigated may have been faulty.
Behçet disease, VKH, sarcoidosis
Authors: KHAIRALLAH M , KAHLOUN R
Published: November 2013

Ocular involvement associated with Behçet disease is characterized by a relapsing remitting panuveitis with diffuse vitritis, retinal infiltrates, and occlusive vasculitis. Proper management relies on the early use of immunosuppressive drugs in combination with corticosteroids and administration of biologic agent in resistant and severe posterior segment involvement. VKH disease is a bilateral panuveitis that may be associated with extraocular manifestations. Exudative retinal detachment, associated with typical imaging findings, is the most specific feature to acute VKH disease. Sunset glow fundus is typical to chronic VKH disease. Complications are more likely to occur in the chronic recurrent phase. The mainstay of treatment for acute VKH disease relies on systemic corticosteroid therapy for at least 6 months. Immunosuppressive therapy is mainly used in chronic recurrent disease. Main ocular features of sarcoidosis include bilateral granulomatous anterior uveitis, vitritis with snowballs, multifocal chorioretinitis, and segmental periphlebitis. Diagnosis may be challenging in the absence of apparent systemic involvement. Treatment of sarcoidosis is based on corticosteroids and immunosuppressive agents, in severe cases.
Optic disc hamartomas in a family with heterozygous mutation in the VMD2 gene: Clinical, diagnostic and molecular genetic findings
Authors: TODOROVA M , SCHORDERET DF , VALMAGGIA C
Published: November 2013

Purpose To report a new form of juvenile‐onset Best disease associated with optic disc deposits and autosomal dominant inheritance in a three‐generation family.

Methods Five affected individuals aged from 5 to 76 years were assessed. Detailed ophthalmic examination including refraction, color fundus photographs, fundus autofluorescence imaging (FAF), optical coherence tomography (OCT), ISCEV‐standard ffERG, mfERG, EOG, as well as ultrasound imaging were performed. Direct sequencing of all exons and intron‐exon junction of the BEST1 gene was conducted.

Results The diagnosis of vitelliform maculopathy was confirmed by clinical and electrophysiological findings supported by genetic analysis. Ophthalmic imaging, OCT and ultrasound imaging showed in four out of five affected members deep subretinal deposits in the macula. Unexpected when the macula was affected, deposits located on the surface of the optic disc, showing the same echography and FAF characteristics, were observed. All five subjects had an abnormal EOG and a normal ffERG. The individual mfERG responses measured in the central, but also in the optic disc areas were reduced, the latencies were delayed. Sequencing revealed a heterozygous c.[670 C>A], coding for a L224M mutation in BEST1 in all affected subjects.

Conclusion Through comparison of the morphological tests: OCT, the FAF ultrasound images and the functional measure: mfERG, we deduct that the observed optic disc deposits are part of generalized disease and have the same origin as the subretinal vitelliform macular and multifocal deposits. This suggests that the described optic disc lesions are vitelliform‐like optic disc hamartomas.
Retinal detachment with PVR
Authors: BERROD JP
Published: November 2013

The goal of surgery for PVR is to reattach the retina by identifying all retinal breaks and relieving all significant vitreoretinal traction. Vitrectomy ,membrane peeling and gas or silicone oil tamponade are required in most cases. Firstly, a meticulous pars plana vitrectomy and shaving of the vitreous base is performed. This is followed by a 360‐degree, scleral‐depressed peripheral retinal examination using a wide‐field viewing system to identify and then diathermize all the retinal breaks. The important goal of PVR surgery is complete membrane peeling to relieve all tangential retinal traction, thus allowing the retina to conform to the RPE/choroid. ILM peeling at the macula is also part of the treatment to prevent pucker formation or redetachment of the macula. In cases where there is persistent traction despite complete membrane peeling a sufficiently large relaxing retinotomy must be performed to relieve the persistant retinal traction. The retina is then temporarily flattened under air ,or perfluorocabon. Next, all of the retinal breaks and edges of any retinotomies are treated confluently with laser. The intraocular gas or silicone oil are typically used to provide extended long term endoretinal tamponade.
New emerging treatments in severe corneal infectious diseases
Authors: GICQUEL J , DUA HS
Published: November 2013

Abstract not provided
Other trans‐trabecular meshwork implants
Authors: LIM K
Published: November 2013

This lecture will review new generation of Trans‐TM devices that are currently in trial or development.

Commercial interest
Effect of neuroprotective statins in retina: A hypercholesterolemic rabbit model
Authors: NAVARRO J , GALLEGO BI , DE HOZ R , RAMIREZ AI , SALAZAR JJ , ROJAS B , TRIVIñO A , RAMIREZ JM
Published: November 2013

Purpose The aim of the present study was to analyze qualitative and quantitative retinal changes in hypercholesterolemic rabbits after a low‐dosage statin treatment and to evaluate their possible neuroprotective effect on the retina.

Methods New Zealand rabbits were divided into three groups: Control (G0; n=6), fed a standard diet; Hypercholesterolemic (G1, n=6), fed a 0.5% cholesterol‐enriched diet for 8 months; and Statins (G2; n=6), fed a 0.5% cholesterol‐enriched diet for 8 months plus administration of fluvastatin sodium or pravastatin sodium at a dosage of 2 mg/Kg/day each. Eyes were processed and analyzed for transmission‐electron microscopy. Semi‐thin sections were used to quantify cell number and thickness of retinal layers (excluding retinal pigment epithelium and nerve‐fiber layer) under light microscopy.

Results G1 and G2, in comparison to G0, had a decreased cell number in the outer nuclear layer (ONL) (p<0.05 and p<0.005, respectively). No differences were detected in the inner nuclear layer or ganglion‐cell layer among the study groups. In G2, the ultrastructural cell morphology was similar to G0 and there were fewer signs of necrosis and apoptosis than in G1. Although the ONL cell number was decreased in G1, the retinal thickness in this group showed no differences in comparison to G0 due to retinal edema. Retinal thickness in G2 was reduced with respect to G1 (p<0.05) because of the absence of retinal edema, and to G0 (p<0.05) due to ONL cell loss.

Conclusion Low‐dosage statins did not prevent ONL cell loss but preserved the normal ultrastructure of the remaining retinal neurons and avoided hypercholesterolemia‐induced retinal edema.
The evolution of monoclonal antibodies
Authors: DICK A
Published: November 2013

Since the Milstein's explosive generation experimentally of monocloncal antibodies both the ability to probe experimentally and deliver therapeutically has created a wave of utilising 'biologics' for therapeutic gain. From understanding of inflammatory responses in the eye during uveitis we have been able to iteratively target either cytokine responses, cell responses or inhibit activation of cells. The introduction will give a brief overview of developments, targets and the future in a more specified and personalised approach to harnessing the strengths of biologic therapy.
Long‐term clinical outcomes in patients with refractory uveitis associated with Behçet's disease treated with infliximab
Authors: ABU EL ASRAR A
Published: November 2013

Purpose: To assess long‐term efficacy and safety of infliximab for refractory Behçet's disease (BD) uveitis and to evaluate the effect of withdrawal of infliximab after achieving long‐term remission. Methods: Retrospective study of 19 patients. Results: Mean follow‐up was 44.1±36.5 months and mean number of infliximab infusions was 21.6 ±14.6. At end of follow‐up, there was significant improvement of visual acuity and reduction of central macular thickness. All patients achieved remission, 14 of whom were able to discontinue corticosteroids. Ten patients developed autoantibodies and one patient developed infusion reactions. Eight eyes underwent intraocular surgery without exacerbation of quiescent uveitis. After achieving complete remission, 5 patients discontinued infliximab and maintained remission during a mean of 24.6 ±5.5 months. Conclusions: Infliximab is effective and safe for long‐term treatment for refractory BD uveitis. Repeated infusions are required to maintain long‐term remission which may be sustained despite withdrawal of infliximab. Induction of autoantibodies is common.