EFSA's OpenFoodTox: An open source toxicological database on chemicals in food and feed and its future developments.

Since its creation in 2002, the European Food Safety Authority (EFSA) has produced risk assessments for over 5000 substances in >2000 Scientific Opinions, Statements and Conclusions through the work of its Scientific Panels, Units and Scientific Committee. OpenFoodTox is an open source toxicological database, available both for download and data visualisation which provides data for all substances evaluated by EFSA including substance characterisation, links to EFSA's outputs, applicable legislations regulations, and a summary of hazard identification and hazard characterisation data for human health, animal health and ecological assessments. The database has been structured using OECD harmonised templates for reporting chemical test summaries (OHTs) to facilitate data sharing with stakeholders with an interest in chemical risk assessment, such as sister agencies, international scientific advisory bodies, and others. This manuscript provides a description of OpenFoodTox including data model, content and tools to download and search the database. Examples of applications of OpenFoodTox in chemical risk assessment are discussed including new quantitative structure-activity relationship (QSAR) models, integration into tools (OECD QSAR Toolbox and AMBIT-2.0), assessment of environmental footprints and testing of threshold of toxicological concern (TTC) values for food related compounds. Finally, future developments for OpenFoodTox 2.0 include the integration of new properties, such as physico-chemical properties, exposure data, toxicokinetic information; and the future integration within in silico modelling platforms such as QSAR models and physiologically-based kinetic models. Such structured in vivo, in vitro and in silico hazard data provide different lines of evidence which can be assembled, weighed and integrated using harmonised Weight of Evidence approaches to support the use of New Approach Methodologies (NAMs) in chemical risk assessment and the reduction of animal testing.

The impact of penetrating keratoplasty in patients with keratoconus using the VF-14 questionnaire.

To assess the visual function of patients with keratoconus who underwent penetrating keratoplasty with the use of the VF-14 questionnaire. Fourteen patients (9 male and 5 female) with a mean age of 38 years (SD 13.59) participated in the study. All patients had keratoconus, confirmed by corneal topography, and all had previously undergone penetrating keratoplasty in one eye. Their mean best-corrected visual acuity (BCVA) binocularly was 0.185 (SD 0.077) LogMAR. None of the grafted eyes had a BCVA < 0.300 LogMAR. Fourteen healthy volunteers, age- and sex-matched, also participated in the study as control subjects. The VF-14 questionnaire was used to evaluate the effect of the ocular status in the daily life activities of the patients. The mean VF-14 result for the grafted patients with keratoconus was 62.37% (SD 22.60) and for the control group it was 100% (P < 0.001). There was only a weak correlation between the VF-14 score and the binocular BCVA (r = -0.394, P = 0.163). The mean VF-14 result in grafted patients with keratoconus is indicative of low functional ability despite the satisfactory postoperative BCVA. The absence of a significant correlation between the VF-14 score and the mean BCVA indicates that the low functional visual ability in these patients is probably associated more with the 'perceived by themselves' difficulty due to their ophthalmological condition.

Viral conjunctivitis interfering with the clinical activity score and management of thyroid ophthalmopathy.

INTRODUCTION: The management of Graves' ophthalmopathy is shared between endocrinologists and ophthalmologists. Assessment and treatment of the active inflammatory stage is based on the clinical activity and disease severity scores, often without detailed eye examination by the treating endocrinologist. MATERIALS AND METHODS: We report a case of acute viral keratoconjunctivitis occurring during immunosuppressive treatment for Graves' ophthalmopathy which masked the signs, symptoms and response to treatment of the orbitopathy, posing a differential diagnostic challenge. RESULTS: The apparent worsening of the ophthalmopathy and the increased clinical activity score led the treating endocrinologist to alter the management decisions. Ophthalmic examination confirmed the diagnosis of viral keratoconjunctivitis and immunosuppressive treatment was continued with significant final improvement of Graves' ophthalmopathy. DISCUSSION: Ocular surface conditions, unrecognised by the treating physician, may complicate the assessment of thyroid ophthalmopathy when detailed eye examination is not performed. The diagnostic challenge of Graves' ophthalmopathy requires a combined approach by an endocrinologist and an ophthalmologist working as a team.

Endothelin-1 concentration is increased in the aqueous humour of patients with exfoliation syndrome.

BACKGROUND: /aim: Endothelin 1 (ET-1) is considered the most potent vasoconstrictor in the body and the eye. This molecule may play a significant role in the pathobiology of exfoliation syndrome (XFS), a disorder characterised by a progressive iris vasculopathy. The purpose of this study was to investigate the concentration of ET-1 in the aqueous humour of cataract patients with and without XFS. METHODS: Aqueous humour samples were obtained from 25 consecutive eyes of 25 cataract patients with XFS and an equal number of age matched controls during phacoemulsification cataract surgery. None of the subjects had elevated intraocular pressure or glaucoma. ET-1 concentration in the aqueous was measured using a specific immunoassay with 100% immunoreactivity for ET-1. Total aqueous humour protein concentration was measured with a microplate Coomassie blue based method and was correlated with ET-1 concentration. RESULTS: Mean ET-1 concentration in the XFS aqueous samples (4.6 (SD 2.3) pg/ml) was significantly higher than that measured in the age matched control samples (2.8 (SD 1.71) pg/ml); (p = 0.006). Although total protein concentration was significantly elevated in the XFS samples (0.380 (SD 0.159) v 0.279 (SD 0.144) mg/ml in the controls); (p = 0.023), no correlation was found between aqueous ET-1 and total protein concentration (p = 0.730). CONCLUSION: The increased concentration of ET-1 in the aqueous humour of XFS patients suggests that ET-1 may play a role in the pathobiology of XFS.

Endogenous group G Streptococcus endophthalmitis following a dental procedure.

PURPOSE: To report a case of bilateral endogenous endophthalmitis due to group G Streptococcus after a dental procedure. METHODS: Case report of a 69-year-old woman who presented with pain, decreased vision, bilateral uveitis, and a unilateral hypopyon 1 week after treatment for an abscessed tooth. RESULTS: Bilateral endophthalmitis was diagnosed, and group G Streptococcus was cultured from the vitreous samples. CONCLUSIONS: To our knowledge, this is the second reported case of endogenous endophthalmitis following a dental procedure. Furthermore, it was due to group G Streptococcus, which is a rare cause of this condition.

Diurnal intraocular pressure reduction with latanoprost 0.005% compared to timolol maleate 0.5% as monotherapy in subjects with exfoliation glaucoma.

AIMS: To compare the diurnal intraocular pressure (IOP) efficacy and safety of timolol vs latanoprost in subjects with exfoliation glaucoma (XFG). METHODS: A 3-month prospective, single-masked, active-controlled, parallel comparison performed in six centres in Greece that randomized subjects in a 1 : 1 ratio to either latanoprost in the evening (2000 hours) and placebo in the morning (0800 hours), or timolol twice daily (0800 and 2000 hours). RESULTS: In all, 103 subjects completed the study. After 3 months of chronic dosing, the latanoprost group exhibited a trend to a greater diurnal IOP reduction from an untreated baseline (24.9+/-3.2-17.4+/-2.9) compared with timolol (24.7+/-2.8-18.3+/-1.9 mmHg) (P=0.07). Latanoprost showed a significantly greater IOP reduction at 0800 hours (-8.5 vs -6.0 mm Hg for timolol, P<0.0001) whereas no difference was observed between the two medications at 1000, 1400, and 2000 hours after a Bonferroni Correction. In addition, latanoprost demonstrated a narrower range of diurnal IOP (2.4) than timolol (3.2 mmHg)(P=0.0017). Safety was similar between groups, except there was more conjunctival hyperaemia with latanoprost (n=8) than timolol (n=1)(P=0.01). CONCLUSIONS: This study suggests that latanoprost provides a statistically lower 08:00-hour IOP and better range of IOP than timolol in the treatment of XFG glaucoma.

8-Isoprostaglandin F2a and ascorbic acid concentration in the aqueous humour of patients with exfoliation syndrome.

BACKGROUND/AIMS: The authors investigated the concentrations of 8-isoprostaglandin F(2a), a marker of oxidative stress in vivo, and ascorbic acid, a protectant against oxidative damage, in the aqueous humour of patients with exfoliation syndrome (XFS) and cataract and compared the results with those in age matched patients with cataract, but without XFS, to determine whether XFS is associated with increased oxidative stress. METHODS: Aqueous humour was aspirated at the beginning of phacoemulsification cataract surgery from 27 eyes of 27 cataract patients with XFS and 27 eyes of 27 age matched cataract patients without XFS. 8-Isoprostaglandin F(2a)concentration in the aqueous was determined with a commercial immunoassay; ascorbic acid concentration was measured with a microplate assay method. RESULTS: The mean concentration of 8-isoprostaglandin F(2a)in the aqueous from patients with XFS (2429 (SD 2940) pg/ml; range 400-10500 pg/ml) was significantly higher than that measured in the aqueous of age matched control patients (529.1 (226.8) pg/ml; range 325-1000 pg/ml); (p = 0.0028). Furthermore, mean ascorbic acid concentration in XFS patients (0.75 (0.39) mM; range 0.28-1.70 mM) was significantly lower than that found in control patients (1.19 (0.47) mM; range 0.53-2.4 mM); (p = 0.0005). There was a reverse correlation between 8-isoprostaglandin F(2a)and ascorbic acid concentration. CONCLUSION: 8-Isoprostaglandin F(2a)was significantly increased in the aqueous of patients with XFS, and ascorbic acid was decreased, providing evidence of a role for free radical induced oxidative damage in the pathobiology of XFS.

Transforming and insulin-like growth factors in the aqueous humour of patients with exfoliation syndrome.

BACKGROUND: Growth factors circulating with the aqueous may play an important role in the pathogenesis of exfoliation syndrome (XFS), which is characterized by excessive synthesis and accumulation of abnormal extracellular material. METHODS: We investigated the concentration of three ubiquitous growth factors (TGF-beta1, TGF-beta2 and IGF-1) in the aqueous humour of 50 patients with XFS (27 from Erlangen, 23 from Thessaloniki) and 54 age-matched controls (27 from Erlangen, 27 from Thessaloniki). This study was performed in two centres, independently of each other, using different assay systems. RESULTS: In the aqueous humour samples collected in Erlangen, both the levels of total TGF-beta1 (P<0.001) and mature TGF-beta1 (P<0.05) were significantly increased in XFS patients compared with controls. Specifically, for total TGF-beta1 patients with XFS exhibited higher a mean value (90.5 +/- 37.4 pg/ml) than controls (30.2 +/- 8.3 pg/ml). The mean level of mature TGF-beta1 was also higher in XFS (14.2 +/- 2.8 pg/ml) than in controls (4.9 +/- 5.5 pg/ml). No difference was found between XFS and controls in the levels of total or mature TGF beta2 in the aqueous or in the level of these two growth factors in the serum. In aqueous humour samples collected in Thessaloniki a significant difference between XFS and controls was also observed for mature TGF-beta1 (XFS 17.06 +/- 11.02 pg/ml vs controls 9.01 +/- 5.69 pg/ml; P=0.006). No difference was observed in TGF-beta2 concentration or IGF-1 concentration in the aqueous. No correlation could be established between protein concentration and the levels of the three growth factors measured. A significant correlation was found between age and protein concentration in XFS, but not in the controls. CONCLUSION: Since TGF-beta1 induces the synthesis and accumulation of extracellular matrix, it is hypothesized that TGF-beta1 plays an important role in the pathogenesis of XFS. Our data suggest that the increased levels of TGF-beta1 are most likely due to enhanced local synthesis.

Genetic evidence for two species of elephant in Africa.

Elephants from the tropical forests of Africa are morphologically distinct from savannah or bush elephants. Dart-biopsy samples from 195 free-ranging African elephants in 21 populations were examined for DNA sequence variation in four nuclear genes (1732 base pairs). Phylogenetic distinctions between African forest elephant and savannah elephant populations corresponded to 58% of the difference in the same genes between elephant genera Loxodonta (African) and Elephas (Asian). Large genetic distance, multiple genetically fixed nucleotide site differences, morphological and habitat distinctions, and extremely limited hybridization of gene flow between forest and savannah elephants support the recognition and conservation management of two African species: Loxodonta africana and Loxodonta cyclotis.

Epiphora caused by conjunctivochalasis: treatment with transplantation of preserved human amniotic membrane.

PURPOSE: To present our experience with the use of preserved human amniotic membrane on patients with epiphora caused by conjunctivochalasis. METHODS: Twelve patients, seven women and five men, ages ranging from 56 to 72 years (mean, 61 years) were referred to our Cornea Service with chronic epiphora. In all patients, no punctal ectropion was present, the lacrimal pathway was patent, and the dye disappearance test was abnormal. All patients had already undergone various therapies including multiple irrigations of the lacrimal system, antibiotic drops, steroid drops, and artificial tear drops. In all patients, conjunctivochalasis, which was not previously diagnosed, was evident on slit-lamp examination. After surgical removal of the excess conjunctiva, preserved human amniotic membrane was placed over and sutured with 10-0 nylon continuous suture to the free conjunctival edges. During the postoperative period, artificial tear drops and steroid/antibiotic drops were applied. RESULTS: Improvement of the epiphora was evident from the first postoperative day. After removal of the suture 10 to 15 days (mean, 12 days) after surgery, no patient complained of epiphora. The dye disappearance test was normal. During the follow-up period, which ranged from 6 to 11 months (mean, 8 months), no patient complained of epiphora and no conjunctivochalasis was detected in the area in which human amniotic membrane was transplanted. CONCLUSION: In our experience, transplantation of preserved human amniotic membrane greatly improved symptoms of epiphora caused by conjunctivochalasis. Continued education of the general ophthalmologists concerning this condition is required.

Isolated ocular ischemic syndrome with no cerebral involvement in common carotid artery occlusion.

PURPOSE: The ocular ischemic syndrome (OIS) is sometimes a complication of common carotid artery (CCA) occlusion causing complete interruption of blood flow through both the internal and external carotid arteries we investigated a single case of an isolated OIS that remained undiagnosed for two years, because the underlying CCA pathology caused no cerebral involvement. CASE REPORT: A 57-year-old man presented with subacute painful visual loss in the right eye in a setting of hypertension, smoking and coronary artery disease. RESULTS. Neurological examination, a brain CT and MRI scan were all normal. Extensive laboratory work-up excluded small artery disease, inflammatory arteritis or cardiac causes of retinal embolism. Ophthalmologic evaluation and fluorescein angiography gave findings consistent with OIS, while vascular ultrasound evaluation and aortic arch angiography verified right CCA occlusion accompanied by an extensive collateral network. CONCLUSIONS: Had this patient been referred sooner for a simple carotid artery work-up, both the CCA occlusion and the OIS could probably had been prevented.

Contact lens fitting difficulties following refractive surgery for high myopia.

PURPOSE: To describe the clinical and optical problems encountered in contact lens fitting following refractive surgery for high myopia. METHODS: Following refractive surgery for high myopia (greater than -10.00 D) we corrected residual refractive errors with contact lenses in the four eyes of two patients. The first patient had undergone bilateral laser in situ keratomileusis (LASIK),with two subsequent LASIK retreatments in the left eye. Ten months later she was fit with rigid gas permeable (RGP) lenses in both eyes. The second patient had undergone a clear lens extraction in the right eye and radial keratotomy followed by photorefractive keratectomy(PRK) in the left eye. She was fit with toric soft lenses six years postoperatively. RESULTS: Final visual acuity obtained with contact lenses was 20/25-20/20 in all eyes. The first patient required significant minus lens power compensation. Furthermore, the RGP lens in the left eye was slightly decentered due to corneal irregularity induced by LASIK. The second patient had regular corneal surfaces and was successfully fit with daily wear toric soft lenses despite the 2.75 D of residual astigmatism in the left eye. CONCLUSIONS: Following refractive surgery for high myopia a proportion of patients will remain undercorrected. In these patients the alterations in corneal architecture that ensue make contact lens fitting more challenging. Patients with regular astigmatism may be fitted successfully with toric soft lenses. Patients with corneal irregularities should be fit with RGP lenses.

Vital signs monitoring from home with open systems.

This study investigates the applicability of a novel codification scheme based on two healthcare informatics standards (namely the VITAL (ENV 13734) and DICOM Sup. 30 Waveform Interchange) in addressing the robust interchange of waveform and medical data in remote healthcare applications. To further address system validation and clinical acceptance issues, pilots were set-up between home-monitoring stations and a hospital-based telemedicine consultation center. The pilots focused in assessing applicability, technical feasibility and performance of the proposed codification scheme based on the two standards. This paper presents the system and services requirements as studied for a home-care application, the design goals for the preservation of security stature, the practical issues of validation and the results of integrating these codification schemes into a commercial patient connected device.

The evaluation of corneal graft tissue by the use of trypan blue.

BACKGROUND: The quality of the donor cornea, which basically depends on the condition of the endothelial sheet, is an important factor for the successful outcome of penetrating keratoplasty. PATIENTS AND METHODS: In this retrospective study, we present our experience in using trypan blue staining for the examination and evaluation of 498 consecutive corneal grafts from 251 donors, concerning their suitability for penetrating keratoplasty, during the decade 1986-1995. RESULTS: Forty-two grafts out of 498 (8.5%) were considered not suitable for surgery because of the great number of destroyed cells (cell density less than 1,500 cells/mm2) and the abnormal cell size and cell shape. Nine out of the 456 (1.97%) operated eyes exhibited primary donor failure and needed re-operation, probably because of boundary cell density of the graft (ranged in those cases from 1,600 to 1,800 cells/mm2). No infections of grafts were observed. CONCLUSION: Tissue evaluation of corneal grafts by the use of trypan blue staining is a simple, cost-effective, safe and accurate method that does not influence the vitality of the endothelial layer of the grafts.

Coralline hydroxyapatite sphere in orbit restoration.

PURPOSE: To restore the anophthalmic socket, primarily or secondarily, using a hydroxy-apatite sphere (HA). METHODS: We used HA in 33 patients (25 male, 8 female), aged from 4 to 68 years (mean 38.1 years) for 19 primary and 14 secondary implantations. HA spheres measured 16 mm in one patient, 18 mm in 21 and 20 mm in 11. The spheres were wrapped in donor sclera preserved in absolute alcohol. All six extraocular muscles were isolated, in the cases where this was possible. Buccal membrane was grafted in three patients to restore the fornices. Drilling was done on four patients using a 3.8 serrated plastic sheath. RESULTS: During follow-up of 7-69 months we observed no complications except for slight edema in the immediate postoperative period. All patients gained very good to excellent motility of the implant, acceptable symmetric appearance in the case of primary implantation, and a dramatic improvement of facial appearance in the case of secondary implantation. CONCLUSIONS: HA spheres are an excellent orbital implant for primary and secondary restoration of the anophthalmic socket causing no serious complications.

Restoration of the anophthalmic socket with secondary implantation of a coralline hydroxyapatite sphere.

BACKGROUND AND OBJECTIVE: Restoration of the anophthalmic socket to improve the aesthetic result on the face. PATIENTS AND METHODS: The authors describe variations in the technique of secondary orbital implantation in 10 patients using the scleral-wrapped hydroxyapatite (HA) sphere implant. Secondary implantation was performed in 4 patients without a previously inserted orbital implant, in 4 patients as an exchange procedure with a preexisting orbital implant, and in 2 patients with eviscerated eyes. Two of these patients proceeded with the drilling operation. RESULTS: All 10 patients achieved a better facial appearance. There were no postoperative complications during the follow-up period of between 6 and 53 months. CONCLUSION: Based on the authors' experience, secondary implantation of the HA sphere is a procedure of choice with no complications, but requires considerable skill and patience on the part of the surgeon.

A simple ocular irrigation system for alkaline burns of the eye.

An alkaline burn of the eye constitutes an ocular emergency. Emergency treatment consisting of copious irrigation begins at the site of the accident and alters the outcome of the injury. The authors describe a low-cost, simple, and effective system for continuous irrigation of the ocular surface after a severe alkaline burn of the eye. This system also can be applied by inexperienced personnel during the transport of a patient to an ophthalmologic center.

Structure and history of African elephant populations: I. Eastern and southern Africa.

Patterns of restriction site variation within mitochondrial DNA (mtDNA) of 270 individuals were used to examine the current structure of savanna elephant populations and to infer historical patterns of gene flow across eastern and southern Africa. Elephants have a complex population structure characterized by marked subdivision at the continental level (Fst = 0.39; 95% confidence interval 0.19-0.58), and isolation by distance at the regional level. However, phylogeographic analysis revealed evidence of protracted gene flow across the continent. First, one relatively derived haplotype was found at all sampling locations. Second, haplotypes representing exceptionally divergent (up to 8.3%) mitochondrial clades were found to coexist at distant (> 2,000 km) sampling locations. In the few other species characterized by sympatric individuals bearing such divergent haplotypes, all such individuals were found to coexist within limited geographical regions. Accordingly, pronounced mitochondrial divergence within populations is often attributed to ancestral isolation in allopatry, followed by secondary contact. The patterns within elephants do not accord with ancestral isolation in allopatry. Given the exceptional mobility of elephants, a geographical barrier is unlikely to have obstructed gene flow between regions for long enough to produce the observed mitochondrial divergence. Rather, the patterns are consistent with the more parsimonious hypothesis, based on neutral coalescent theory, that gene flow has maintained a sufficiently large effective population size (> 50,000 females) for representatives of clades that diverged at least 4 million years ago to have persisted by chance within a population that was subdivided, but not strictly isolated in allopatry.

Management of pseudophakic retinal detachment with various intraocular lens types.

In the last five years, 25 cases of retinal detachment (RD) after intraocular lens implantation were treated in the University Eye Clinic of Thessaloniki. The incidence of RD was lower with posterior chamber intraocular lens (PC-IOL, 0.46%) implantation than in the cases with anterior chamber IOL (AC-IOL, 2.6%) implantation. The successful reattachment rate was higher with PC-IOL (100%) than in cases with AC-IOL where the low success (87%) rate was caused by proliferative vitreoretinopathy. Therefore, the eyes with AC-IOL required reoperation more frequently, and the ultimate failure rate (despite multiple operations) was higher in the AC-IOL group. Conventional surgical techniques were used in the first procedure. In the reoperated cases, the most advanced techniques were used, such as vitrectomy combined with gas or silicone oil injection.