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Background Being born large for gestational age ( LGA) is a marker of increased growth velocity in fetal life and a risk factor for childhood overweight. Both being born LGA and childhood overweight may influence the development of asthma, although the role of overweight in the association between LGA and childhood asthma is unclear. Importantly, recent studies have suggested that the association between overweight and asthma may be related to non-allergic pathways. If this also applies to the association between LGA and asthma, the association between being born LGA and asthma may be different for atopic and non-atopic children. Objective We investigated the association of being LGA with the prevalence of asthma at age 8 in atopic and non-atopic children and the role of overweight in this association. Methods Complete data on asthma, anthropometry and atopy at age of 8 years, and potential confounders were available for 1608 participants of the PIAMA birth cohort. Odds ratios for the association between LGA and asthma in atopic and non-atopic children were estimated by logistic regression analysis adjusting for potential confounders. Overweight was assessed as a potential modifier of the association between LGA and asthma. Results Being born LGA was not significantly associated with asthma at age of 8 in atopic and non-atopic children. However, overweight at age of 8 years modified the association between asthma at age of 8 and LGA. In non-atopic children, children who were born LGA and were overweight at age of 8 years had a significantly increased odds of asthma compared to non- LGA, non-overweight children (adj OR 7.04; 95% CI 2.2-24). Conclusions We observed that non-atopic children born LGA, who were overweight by 8 years have an increased risk of asthma. If confirmed, these findings suggest that non-atopic children born LGA may be identified early in life as a high-risk group for asthma. [ABSTRACT FROM AUTHOR]

Background/purpose When evaluating skin care products for human skin, quantitative test methods need to be simple, precise and reliable. Optical coherence tomography ( OCT), provides high-resolution sectional images of translucent materials to a depth of a few millimeters, a technique usually applied to medical measurements in ophthalmology and dermatology. This study aimed to demonstrate the application of OCT as the main technique for monitoring changes in skin topography during tests of a wrinkle-reduction product in humans. Methods We used a commercial OCT apparatus to perform clinical examinations of skin roughness in treated and non-treated sites in the periorbital region of thirty human voluntaries who were using an anti-aging product commercially available: Natura Chronos® Flavonóides de Passiflora 45+ FPS15, from Natura Cosméticos, Brazil. Measurements were performed days 0, 7, 14 and 28 of treatment. Equipment and software allowed real-time recording of skin roughness parameters and wrinkle depths. Results The OCT measurements have allowed the monitoring of changes in skin roughness, which have shown reduction in treated sites around 10%. The obtained depth distributions also indicate reduction in the occurrence of wrinkles deeper than 170 μm. The verified results are consistent with those typically obtained after successful treatment with modern anti-aging products. Conclusion By using the OCT technique, it was possible to quantify changes in skin roughness and in the distribution of depths of skin wrinkles, with adequate sensitivity. OCT imaging allows the direct visualization of the skin topography with resolution of micrometers, a reliable and interactive tool for clinical use. Therefore, for the first time, we demonstrated the use of OCT technique to verify the efficacy of cosmetic products in real time. [ABSTRACT FROM AUTHOR]

. Purpose: To determine whether retinal vessel oxygen saturation in patients with glaucoma is associated with structural optic disc and retinal nerve fibre layer (RNFL) changes and visual field (VF) defects. Methods: Fifty-nine patients with confirmed glaucoma were recruited at University Hospitals Leuven. Retinal oxygen saturation in patients with glaucoma was measured with a noninvasive spectrophotometric retinal oximeter (Oxymap ehf, Reykjavik, Iceland). VF and Heidelberg retinal tomographies (HRTs) were performed on the same day. Statistical analysis was performed using Student's t-test and Pearson's or Spearman correlation coefficient. Results: The mean oxygen saturation in venules was higher in patients with severe VF defects compared to those patients with mild VF defects (69 ± 3% versus 65 ± 6% respectively; p = 0.0003; n = 59). Accordingly, the arteriovenous (AV) difference in oxygen saturation was lower in patients with worse VF compared to those with better VF (29 ± 3% versus 33 ± 6% respectively; p = 0.002). The oxygen saturation in venules correlated with the VF mean defects ( r = −0.42; p = 0.001; n = 59) as well as with the structural HRT parameters rim area and RNFL thickness ( r = −0.39; p = 0.008 and r = −0.26; p = 0.05 respectively; n = 53). The AV difference decreased significantly as the VF defect worsened ( r = 0.38; p = 0.003), as the rim area diminished ( r = 0.29; p = 0.03) and as the RNFL thickness decreased ( r = 0.27; p = 0.05). No correlation was found between the oxygen saturation in retinal arterioles and either of these parameters. Conclusion: Severe glaucomatous damage is associated with increased oxygen saturation in retinal venules and decreased AV difference in oxygen saturation. These data suggest that in eyes with severe glaucomatous damage, reduced retinal oxygen consumption is consistent with tissue loss. [ABSTRACT FROM AUTHOR]

Background Interferon-regulatory factors ( IRFs) play a crucial role in immunity, not only influencing interferon expression but also T cell differentiation. IRF-4 was only recently recognized as a further major player in T cell differentiation. Objective As IRF-1 polymorphisms were shown to be associated with atopy and allergy, we comprehensively investigated effects of IRF-4 variants on allergy, asthma and related phenotypes in German children. Methods Fifteen tagging single nucleotide polymorphisms (SNPs) in the IRF-4 gene were genotyped by MALDI- TOF MS in the cross-sectional ISAAC phase II study population from Munich and Dresden (age 9-11; N = 3099). Replication was performed in our previously established genome-wide association study ( GWAS) data set ( N = 1303) consisting of asthma cases from the Multicenter Asthma Genetic in Childhood ( MAGIC) study and reference children from the ISAAC II study. Results SNPs were not significantly associated with asthma but with bronchial hyperresponsiveness, atopy and, most interestingly, with recurrent bronchitis in the first data set. The IRF-4 variant rs9378805 was associated with recurrent bronchitis in the ISAAC population and replicated in the GWAS data set where further SNPs showed associations with recurrent bronchitis and asthma. Conclusions We found genetic associations in IRF-4 to be associated with recurrent bronchitis in our two study populations. Associated polymorphisms are localized in a putative regulatory element in the 3′ UTR region of IRF-4. These findings suggest a putative role of IRF-4 in the development of bronchitis. [ABSTRACT FROM AUTHOR]

J Oral Pathol Med (2010) 39 176–181 Background: Local failure occurs in 13.9–62.6% and it is a well known indicator of poor prognosis in patients with oral squamous cell carcinoma (OSCC), despite aggressive treatments. The purpose of this study was to investigate the value of histopathology and molecular biomarkers in predicting the development of early local recurrence. Methods: This study included a total of 69 patients. There were 23 patients with early recurrent OSCC and 46 patients without local recurrence with the same clinical stage and tumor site, in a pair-matched study design. Their charts were retrospectively analyzed. All surgical specimens of the primary tumors were evaluated according to the system proposed by Anneroth et al. and immunohistochemical for ErbB2 and FAS were performed. Results: A significant correlation of early local recurrence with grade of histological malignancy (more than 15 points) was observed (Fisher’s exact test, P = 0.03). Early local recurrence was also significantly associated with weak FAS expression and strong intracytoplasmic ErbB2 staining (Mantel–Haenszal chi-square, P = 0.0038 and P = 0.0068, respectively). Histological grade of malignancy (more than 15 points) was also correlated with reduced survival (log-rank, P = 0.06). Among the histopathological parameters, keratinization, pattern of invasion and inflammation were important for overall survival (log-rank, P < 0.0001). Regarding the biomarkers, only FAS was significantly associated with overall survival (log-rank, P = 0.0002). Moreover, a positive correlation of FAS and membrane ErbB2 expression with keratinization was noticed. Conclusion: Histopathological characteristics and the expression of FAS and ErbB2 carry prognosis importance in local recurrence and overall survival in OSCC. [ABSTRACT FROM AUTHOR]

Background: Allergic inflammation can trigger neuronal dysfunction and structural changes in the airways and the skin. Levels of brain-derived neurotrophic factor (BDNF) are strongly up regulated at the location of allergic inflammation. Aim: We systematically investigated whether polymorphisms in the BDNF gene influence the development or severity of asthma and atopic diseases. Methods: The BDNF gene was screened for mutations in 80 chromosomes. Genotyping of six BDNF tagging polymorphisms was performed in a cross-sectional study population of 3099 children from Dresden and Munich (age 9–11 years, ISAAC II). Furthermore, polymorphisms were also investigated in an additional 655 asthma cases analysed with a random sample of 767 children selected from ISAAC II. Associations were calculated via chi-square test andanova using SAS Genetics andspss. Results: We identified nine polymorphisms with minor allele frequency ≥0.03, one of them leading to an amino acid change from Valine to Methionine. In the cross-sectional study population, no significant association was found with asthma or any atopic disease. However, when more severe asthma cases from the MAGIC study were analysed, significant asthma effects were observed with rs6265 (odds ratio 1.37, 95% confidence interval 1.14–1.64, P = 0.001), rs11030101 (OR 0.82, 95%CI 0.70–0.95, P = 0.009) and rs11030100 (OR 1.19, 95%CI 1.00–1.42, P = 0.05). Conclusions: As in previous studies, effects of BDNF polymorphisms on asthma remain controversial. The data may suggest that BDNF polymorphisms contribute to severe forms of asthma. [ABSTRACT FROM AUTHOR]

Background: Interleukin 15 (IL15) promotes activation and proliferation of CD8+ T cells and enhances the differentiation into Th2 cells. A previous study described five polymorphisms in the IL15 gene to be associated with asthma in a haplotype analysis. Aim: We selected HapMap tagging single nucleotide polymorphisms (SNPs) from IL15 to systematically investigate these IL15 associations in a large population-based sample. Methods: Genotyping of seven IL15 SNPs was performed using MALDI-TOF MS in a cross-sectional study population of 3099 children from Dresden or Munich (age 9–11 years). All children were phenotyped by standardized and validated protocols for atopic phenotypes. Effects of single SNPs and haplotypes were studied usingsas 9.1.3 andhaploview. Equivalence tests were performed to prove the significance of negative results. Results: Neither single IL15 polymorphisms nor haplotype analyses showed associations with asthma or atopy after correction for multiple testing. Conclusion: These results do not confirm previous case–control studies and suggest that IL15 gene variants do not play an important role in the development for asthma or other atopic disorders. [ABSTRACT FROM AUTHOR]

Background: Signal transducer and activator of transcription 1 (STAT1), an intracellular signal transducer and activator of transcription centrally involved in many inflammatory pathways, was recently suggested to play an important role in allergy related immune responses. Aim: Thus, we investigated the effect of polymorphisms in the STAT1 gene on the development of atopic sensitization and allergic diseases. Methods: Haplotype tagging single nucleotide polymorphisms (SNPs) previously described in the STAT1 gene were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry technology in a cross-sectional study population of 3099 German children recruited and phenotyped by the International Study of Asthma and Allergy in Childhood, phase II (ISAAC II). Effects of single SNPs and haplotypes were studied using SAS/Genetics and Haploview. Results: The polymorphism C39134A (rs3771300), located in a potentially cis acting regulatory element in STAT1 intron 24, was inversely related to atopy measured by skin prick test, total and specific serum IgE levels while no effect on atopic disease risk was observed. Conclusion: Our results indicate that STAT1 SNP C39134A may protect from atopic sensitization. Because of its location in a highly conserved noncoding sequence near a putative GATA3 binding site, this polymorphism represents an interesting target for further studies. [ABSTRACT FROM AUTHOR]

Microsatellites or simple sequence repeats (SSRs) are one of the most suitable markers for genome analysis as they have great potential to aid breeders to develop new improved sugarcane varieties. The development of SSR derived from expressed sequence tags (EST) opens new opportunities for genetic investigations at a functional level. In the present work, the polymorphism obtained with a subset of 51 EST–SSRs derived fromsucest was compared with those generated by 50 genomic SSRs (gSSR) in terms of number of alleles, polymorphism information content, discrimination power and their ability to establish genetic relationships among 18 sugarcane clones including three Saccharum species ( S. officinarum, S. barberi, S. sinense). The majority of EST–SSRs loci had four to six alleles in contrast to the seven to nine observed for the gSSRs loci. Approximately, 35% of the gSSRs had PIC values around 0.90 in contrast to 15% of the EST–SSRs. However, the mean discrimination power of the two types of SSR did not differ significantly as much as the average genetic similarity (GS) based on Dice coefficient. The correlation between GS of the two types of SSRs was high ( r = 0.71/P = 0.99) and significant. Although differences were observed between dendrograms obtained with each SSR type, both were in good agreement with pedigree information. The S. officinarum clone IJ76-314 was grouped apart from the other clones evaluated. The results here demonstrate that EST–SSRs can be successfully used for genetic relationship analysis, extending the knowledge of genetic diversity of sugarcane to a functional level. [ABSTRACT FROM AUTHOR]

T- lymphocyte activation is accompanied by a loss of CD45RA determinant and gain of CD4SRO marker. Previous work suggests that the CD45RO population could represent the T-cell memory pool since it contains most of the cells that can respond to recall soluble antigens. A selective loss of memory T cells was recently found in early stages of human immunodeficiency virus (HIV) infection, which could contribute to the qualitative defects observed in HIV-infected patients. In order to investigate whether HIV infection could induce an alteration in the process of differentiation from naive cells to cells with a memory phenotype, we studied the expression of CD45RA and CD45RO in CD4+ and CD8+ lymphocytes, by flow cytometric analysis, after mitogenic stimulation of mononuclear cells from patients with HIV infection. These preliminary results suggest that after in vitro activation the CD4+ and CD8+ populations from HIV-infected patients lose the CD4SRA marker and concomitantly acquire the CD45RO determinant in the same way as shown for the healthy control population studied simultaneously. Thus, it appears that an alteration in the process of conversion of CD45RA into CD45RO does not contribute to the defects observed in the memory T-cell population in HIV infection. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented concerning smoking cessation, focusing on India.

Dupilumab, blocking IL‐4 and IL‐13 signals, improves atopic dermatitis and Quality of Life but might be also associated with the occurrence of ocular adverse events (OAEs). The main objective of our prospective study was to characterize the cytokine and chemokine profile in the tear fluid of dupilumab‐treated patients with moderate‐to‐ severe atopic dermatitis and to identify biomarkers predicting the occurrence of ocular adverse events. Patients with moderate‐to‐severe AD underwent dermatological and ophthalmological evaluation at the baseline (T0) and week 16 or at the time of an eventual ocular adverse events (T1). A multiplex immunoassay measuring multiple cytokines and chemokines in the tear fluid extracted during ocular examination at both T0 and T1 was performed. Thirty‐nine patients with moderate‐to‐severe AD and treated with dupilumab were included in the study. Baseline tear fluid levels revealed a significantly higher concentration of type 2 cytokines and chemokines in AD patients than healthy controls. The occurrence of ocular adverse events during dupilumab therapy was associated with a significant increase of IL‐33 tear fluid levels and a significantly lower tear break‐up time, this latter also identified as predictive factor. Our findings suggest that the ophthalmological examination should be considered a valid support to identify patients at risk of developing OAEs and to provide their appropriate management. [ABSTRACT FROM AUTHOR]

This article reports on two cases of successful treatment with tralokinumab in patients with atopic dermatitis (AD) and dupilumab-induced psoriasis. The first case involves a 75-year-old woman who experienced psoriatic lesions after receiving dupilumab treatment. Methotrexate was added to manage the psoriatic eruption, but it was discontinued due to side effects. Tralokinumab was then started, resulting in the resolution of both AD and psoriatic lesions. The second case involves an 18-year-old woman who also developed psoriasis while on dupilumab. Tralokinumab was started after topical steroids showed minimal improvement, leading to remission of the psoriatic lesions and maintenance of AD remission. The article suggests that tralokinumab may be a valid option for treating AD in patients with dupilumab-induced psoriasis. [Extracted from the article]

Research for autonomic nervous system dysfunctions ( ANS) in glaucoma patients has a two-fold interest for the glaucoma specialist. On one hand, it provides the physician with a set of results that demonstrate the extent of the underlying systemic and ocular dysfunction. These data may provide clues as to why the disease is continuing to progress and may therefore help guide glaucoma management. While strategies towards correcting these imbalances have not been definitely proven to affect the outcome of glaucoma, there are an increasing number of anedoctal data that suggests they may have a positive impact in disease progression. Moreover, signalling the extent of the systemic dysregulation may help identify other, non-ocular related problems and thus be ultimately beneficial to the patients in the long term. More research is still needed to idenfity which patients are more likely to benefict from undergoing ANS function tests and - should any dysfunction be found - what would be the most consistent treatment strategy. [ABSTRACT FROM AUTHOR]

Purpose Glaucoma patients are known to have an underlying vascular dysfunction and General anesthesia ( GA) significantly decreases blood pressure, which might decrease ocular perfusion. This study was conducted to investigate the effects of GA on ophthalmic flow velocities and blood pressure. Methods Prospective, case-control study. Glaucoma patients were scheduled for trabeculectomy or drainage device implantation; non-glaucomatous patients undergoing vitrectomy for macular hole or epiretinal membrane peeling were recruited as control subjects. Color Doppler imaging of the ophthalmic artery ( OA) was performed immediately before and 1 minute after GA induction. The following parameters were analyzed: OA blood velocities and resistivity index, as well as cardiovascular parameters (diastolic and systolic blood pressure and heart rate). Statistical analysis was performed using Student’s paired t test, Mann-Whitney, Fisher's exact test and Spearman's correlation. Results 53 patients were included (glaucoma group: 25; control group: 28). The magnitude in blood pressure decrease after GA induction was similar between the two groups (p value 0.61-0.70). However, the decrease in OA blood velocities was significantly larger in the glaucoma groups than in the control group (p < 0.03 in all comparisons). Unlike the control subjects, in the glaucoma group there was a significant association between the magnitude of blood pressure decrease and the lowering of the OA mean blood velocity ( r = 0.69, 95% IC: 0.36-0.87, p < 0.001). Conclusions These results suggest that glaucoma patients are unable to keep a stable blood velocity in the OA when subjected to acute significant decreases in blood pressure (such as the ones seen after GA induction). [ABSTRACT FROM AUTHOR]

Purpose Glaucoma is known to be associated with vascular dysfunction. However, integrating this knowledge in the clinical setting has been limited, considering the majority of vascular oriented studies have been either underpowered or only addressed a small segment of the vascular parameters in strictly selected patients. The Leuven Eye Study aims at bridging this gap by prospectively collecting the largest amount of vascular oriented data in a large real-life glaucoma clinic setting. Methods Prospective, cross-sectional, case-control hospital-based study. Patients with primary open-angle glaucoma ( POAG), normal tension glaucoma ( NTG), glaucoma suspect or ocular hypertension ( OHT) and healthy volunteers were recruited. In addition to an ophthalmological examination, a vascular-oriented questionnaire was completed and ocular blood flow assessment (color Doppler imaging of retrobulbar vessels, retinal oximetry, dynamic contour tonometry, optical coherent tomography enhanced depth imaging of the choroid) was performed in each subject. Results 620 subjects (297 male) were recruited between March and December 2013 ( POAG: 214, NTG: 192; glaucoma suspect: 41; OHT: 27; healthy controls: 146). Mean age was 68.4 ± 12.9 years. Other than IOP, there was no difference in demographic variables between glaucoma groups and healthy volunteers. Values for the ocular blood flow parameters are in line with the current literature. Conclusions The Leuven Eye study stands as the largest clinical trial on ocular blood flow in glaucoma. The creation of this vast database may help integrate the vascular aspects of glaucoma into the clinical practice of glaucoma. [ABSTRACT FROM AUTHOR]

Purpose To investigate the correlation between cerebral tissue oxygenation (SctO2) and retinal vessel oxygen saturation (SO2) using non-invasive spectroscopy in healthy individuals. Methods Retinal and cerebral oxygen saturations were measured in dark-adapted, healthy volunteers breathing ambient air in a seated position using dual wavelength retinal oximetry and transcranial near-infrared spectroscopy (NIRS) respectively. Correlations between SO2 and SctO2 were analyzed using Pearson correlation coefficients. Multivariate analysis was performed to determine the relative contribution of the arterial and venous vessels to SctO2. Using this model, SctO2 was estimated based on retinal arterial and venous oxygen saturation. Pearson correlation coefficients, paired sample t-test and Bland-Altman analysis were used to assess the agreement between the measured and the predicted SctO2. Results Twenty-one young healthy individuals aged 26.4 ± 2.2 years were analyzed. SctO2 showed a significant positive correlation with both arterial and venous SO2 (r = 0.442, P = 0.045 and r = 0.434 P = 0.049 respectively). In multivariate analysis, the relative contribution of arterial and venous SO2 to SctO2 was significantly correlated with diastolic blood pressure, retinal venous oxygen saturation and retinal venous diameter (R2=0.60, P < 0.001). The measured SctO2 (72.2 ± 3.5%, range 67.3-80.1) correlated well with estimated SctO2 (72.2 ± 2.6%, range 67.6-77.5) (r = 0.774, P < 0.001). Bland-Altman plots showed 95% agreement within ±6.8%. Conclusions In this pilot study, retinal oximetry showed promising as an estimate of cerebral tissue oxygenation as measured by NIRS. [ABSTRACT FROM AUTHOR]

Purpose Glaucoma is known to be associated with vascular dysfunction. However, integrating this knowledge in the clinical setting has been limited, considering the majority of vascular oriented studies have been either underpowered or only addressed a small segment of the vascular parameters in strictly selected patients. The Leuven Eye Study aims at bridging this gap by prospectively collecting the largest amount of vascular oriented data in a large real-life glaucoma clinic setting. Methods Prospective, cross-sectional, case-control hospital-based study. Patients with primary open-angle glaucoma ( POAG), normal tension glaucoma ( NTG), glaucoma suspect or ocular hypertension ( OHT) and healthy volunteers were recruited. In addition to an ophthalmological examination, a vascular-oriented questionnaire was completed and ocular blood flow assessment (color Doppler imaging of retrobulbar vessels, retinal oximetry, dynamic contour tonometry, optical coherent tomography enhanced depth imaging of the choroid) was performed in each subject. Results 620 subjects (297 male) were recruited between March and December 2013 ( POAG: 214, NTG: 192; glaucoma suspect: 41; OHT: 27; healthy controls: 146). Mean age was 68.4 ± 12.9 years. Other than IOP, there was no difference in demographic variables between glaucoma groups and healthy volunteers. Values for the ocular blood flow parameters are in line with the current literature. Conclusions The Leuven Eye study stands as the largest clinical trial on ocular blood flow in glaucoma. The creation of this vast database may help integrate the vascular aspects of glaucoma into the clinical practice of glaucoma. [ABSTRACT FROM AUTHOR]

Background: Positive fluid balance (FB) is associated with poor outcomes in critically ill children but has not been studied in pediatric liver transplant (LT) recipients. Our goal is to investigate the relationship between postoperative FB and outcomes in pediatric LT recipients. Methods: We performed a retrospective cohort study of first‐time pediatric LT recipients at a quaternary care children's hospital. Patients were stratified into three groups based on their FB in the first 72 h postoperatively: <10%, 10–20%, and > 20%. Outcomes were pediatric intensive care unit (PICU) and hospital length of stay, ventilator‐free days (VFD) at 28 days, day 3 severe acute kidney injury, and postoperative complications. Multivariate analyses were adjusted for age, preoperative admission status, and Pediatric Risk of Mortality (PRISM)‐III score. Results: We included 129 patients with median PRISM‐III score of 9 (interquartile range, IQR 7–15) and calculated Pediatric End‐stage Liver Disease score of 15 (IQR 2–23). A total of 37 patients (28.7%) had 10–20% FB, and 26 (20.2%) had >20% FB. Greater than 20% FB was associated with an increased likelihood of an additional PICU day (adjusted incident rate ratio [aIRR] 1.62, 95% CI: 1.18–2.24), an additional hospital day (aIRR 1.39, 95% CI: 1.10–1.77), and lower likelihood of a VFD at 28 days (aIRR 0.85, 95% CI: 0.74–0.97). There were no differences between groups in the likelihood of postoperative complications. Conclusions: In pediatric LT recipients, >20% FB at 72 h postoperatively is associated with increased morbidities, independent of age and severity of illness. Additional studies are needed to explore the impact of fluid management strategies on outcomes. [ABSTRACT FROM AUTHOR]

Objective To evaluate the antiinflammatory effects of RC-3095 in 2 experimental models of arthritis, collagen-induced arthritis (CIA) and antigen-induced arthritis (AIA), and to determine the mechanisms of action involved. Methods RC-3095 was administered daily to mice with CIA and mice with AIA, after induction of disease with methylated bovine serum albumin. Disease incidence and severity were assessed using a clinical index and evaluation of histologic features, respectively. In mice with CIA, gastrin-releasing peptide receptor (GRPR) was detected by immunohistochemical analysis, while in mice with AIA, migration of neutrophils, presence of glycosaminoglycans, and lymphocyte proliferation, determined using the MTT assay, were assessed. Expression of cytokines interleukin-17 (IL-17), IL-1β, and tumor necrosis factor α (TNFα) was evaluated in all mouse knees using enzyme-linked immunosorbent assay. Treg cell production was assessed by flow cytometry in the joints of mice with AIA. Results In mice with AIA, administration of RC-3095 reduced neutrophil migration, mechanical hypernociception, and proteoglycan loss. These findings were associated with inhibition of the levels of all 3 proinflammatory cytokines, decreased lymphocyte proliferation, and increased Treg cell numbers. In the CIA model, treatment with RC-3095 led to a significant reduction in arthritis clinical scores and the severity of disease determined histologically. Synovial inflammation, synovial hyperplasia, pannus formation, and extensive erosive changes were all dramatically reduced in the arthritic mice treated with RC-3095. Furthermore, arthritic mice treated with RC-3095 showed a significant reduction in the concentrations of IL-17, IL-1β, and TNFα, and showed a diminished expression of GRPR. Conclusion These findings suggest that the GRP pathway has a significant role in chronic arthritis, and its inhibition can be explored as a possible therapeutic strategy in rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Topiramate was associated with weight loss in clinical trials. We summarize the evidence on the efficacy and safety of topiramate in the treatment of overweight/obesity. The databases Medline, Embase, and Cochrane were searched. Randomized controlled studies with at least 16 weeks of duration that report the effect of topiramate on weight loss and adverse events were eligible for inclusion. Ten studies were included (3320 individuals). Patients treated with topiramate lost an average of 5.34 kg (95% confidence interval [95%CI]−6.12 to −4.56) of additional weight as compared with placebo. According to meta-regression analysis, treatment duration and dosage were associated with the efficacy of topiramate treatment. Evaluating trials using topiramate 96-200 mg day, the weight loss was higher in trials with >28 weeks of duration (−6.58 kg [95%CI −7.48 to −5.68]) than in trials with ≤28 weeks (−4.11 kg [95%CI −4.92 to −3.30]). Data of 6620 individuals were available for adverse events evaluation and those more frequently observed were paraesthesia, taste impairment and psychomotor disturbances. The odds ratio for adverse events leading to topiramate withdrawal was 1.94 (95%CI 1.64-2.29) compared with the control group. In conclusion, topiramate might be a useful adjunctive therapeutic tool in the treatment of obesity as long as proper warnings about side effects are considered. [ABSTRACT FROM AUTHOR]

Chronic stress is a powerful modulator of emotional behaviour. Previous studies have shown that distinct neuronal pathways modulate different emotional behaviours: while the amygdala plays a key role in fear-conditioned-to-cue stimuli, the bed nucleus of stria terminalis (BNST) is implicated in anxiety behaviour and responses to contextual stimuli. In addition, the BNST is directly involved in the regulation of the hypothalamus–pituitary–adrenal (HPA) axis. In the present study, we assessed anxiety (measured in the elevated-plus maze and acoustic startle apparatus) and fear-conditioned responses to light stimuli in rats that had been exposed to either chronic unpredictable stress or corticosterone for 28 days; thereafter, stereological estimates of the BNST and amygdaloid complex were performed, followed by three-dimensional morphometric dendritic analysis. Results show that chronic stress induces hyperanxiety without influencing fear conditioning or locomotion and exploratory activity. Stress-induced hyperanxiety was correlated with increased volumes of the BNST but not of the amygdala. Dendritic remodelling was found to make a significant contribution to the stress-induced increase in BNST volume, primarily due to changes in the anteromedial area of the BNST, an area strongly implicated in emotional behaviour and in the neuroendocrine control of the stress response. Importantly, all of the effects of stress were recapitulated by exogenous corticosterone. In conclusion, this study shows that chronic stress impacts on BNST structure and function; its findings pertain to the modulation of emotional behaviour and the maladaptive response to stress. [ABSTRACT FROM AUTHOR]

Summary: Identifying genes or genomic regions influencing carcass‐quality traits such as fatness (FTN) is essential to optimize the genetic selection processes in beef cattle. The aim of this study was to identify genomic regions associated with FTN in Nellore cattle as well as to elucidate the metabolic pathways related to the phenotypic expression. Ultrasound‐based measurements of FTN were collected in 11 750 animals, with 39 903 animals in the pedigree file. Additionally, 1440 animals were genotyped using the GGP‐indicus 35K SNP panel, which contained 33 623 SNPs after quality control. Twenty genes related to FTN were found on 11 chromosomes, explaining 12.96% of the total additive genetic variance. Gene ontology revealed seven genes: NR1L2, PKD2, GSK3β, EXT1, RAD51B, SORCS1 and DPH6, associated with important processes related to FTN. In addition, novel candidate genes (MAATS1, LYPD1, CDK5RAP2, RAD51B, c13H2Oorf96 and TRAPPC11) were detected and could provide further knowledge to uncover genetic regions associated to carcass fatness in beef cattle. [ABSTRACT FROM AUTHOR]

Aim: To compare the immunoexpression of RANK, MMP‐9 and PTHrP in apical periodontitis lesions of diabetic and normoglycaemic individuals. Methodology: Primary chronic apical periodontitis lesions associated with teeth indicated for extraction in 13 type 2 diabetic individuals and 13 normoglycaemic individuals who were screened for the glycaemic index and glycated haemoglobin (HbA1c) were analysed. Individuals with other systemic diseases and users of anti‐inflammatories and/or antibiotics in the previous 3 months were excluded. Silanized slides with paraffin sections were used for immunohistochemical reactions and stained with haematoxylin and eosin for histopathological classification. The images were analysed with an optical microscope, and the slides were subdivided into five large fields assigning scores (0–2), according to the number of positive markings for each antibody. Fisher's exact test evaluated the parameters: gender, type of lesion, location and position in the arch. Nonparametric Mann–Whitney test was used for age, HbA1c values and comparison of marker expression. The chi‐squared test was used to associate the expression of the markers. And the Spearman's coefficient correlated the markers with the size of the periapical lesion. Results: The samples consisted of 69% periapical granulomas and 31% periapical cysts in each group. RANK expression was considered weak/moderate and strong in, respectively, 62% and 38% of the cases in both groups. MMP‐9 expression was weak/moderate and strong in, respectively, 38% and 62% of the cases from the diabetic group, in comparison with 38% and 38% in the normoglycaemics (24% cases from this group were negative). In contrast, PTHrP expression was negative, weak/moderate and strong in, respectively, 46%, 46% and 8% of the cases from the diabetic group, in comparison with 38% negative and 62% weak/moderate in normoglycaemics. Quantitative analysis revealed that there were no significant differences in the immunoexpression of RANK (P = 0.26), MMP‐9 (P = 0.17) and PTHrP (P = 0.43) between the groups. There was no significant correlation between the expression of bone resorption markers and the macroscopic size of the periapical lesions (P > 0.05). Conclusions: The bone resorption mediators analysed had similar immunoexpression in the periapical lesions of diabetic and normoglycaemic individuals. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the degree of surgically induced corneal astigmatism (SIA) following trabeculectomy and to investigate the relation of SIA with long-term reduction of intraocular pressure (IOP). Methods Forty-four eyes of 44 patients undergoing fornix-based trabeculectomy were included in this single center, prospective trial. IOP, visual acuity (VA), corneal astigmatism, medication use and adverse events were recorded preoperatively and at 1, 3, 6 and 18 months postoperatively. Changes in corneal astigmatism were analysed using vector analysis. Pre- and postoperative parameters were compaired using one-sample t-test. Correlation between SIA and IOP were assessed using Pearson correlation coefficients. Results Vector analysis of corneal astigmatism revealed a significant increase in with-the-rule corneal astigmatism, reaching a maximum at 1 month postoperatively (1.15 ± 0.8 D, P < 0.001) followed by a gradual decline (0.87 ± 0.8 D, P < 0.001 at month 18). SIA at 1 month showed a borderline significant correlation with IOP reduction at 3 months (r = 0.315, P = 0.051). SIA at 3, 6 and 18 months did not correlate with reduction in IOP (P > 0.05). After a transient decline at 1 month after surgery, VA recovered to preoperative values at month 3 without need for adjustment of the optical correction. Conclusions Fornix-based trabeculectomy induces statistically significant with-the-rule astigmatism without affecting long term VA. In our population, maximum SIA, measured at 1 month postoperatively, showed a borderline significant correlation with reduction of IOP at 3 months. [ABSTRACT FROM AUTHOR]

Background and Purpose: IL-33 signals through ST2 receptors and induces adaptive and innate inflammation. IL-33/ST2 is involved in adaptive inflammation-induced pain. Here, we have investigated the contribution of IL-33/ST2-triggered mechanisms to carrageenin-induced innate inflammation.Experimental Approach: Carrageenin- and IL-33-induced inflammatory responses were assessed in BALB/c- (WT) and ST2-deficient ((-/-) ) mice as follows: oedema (plethysmometer), myeloperoxidase activity (colorimetric assay), mechanical hyperalgesia (electronic version of von Frey filaments), cytokine levels (ELISA), PGE2 (RIA), mRNA expression (quantitative PCR), drug treatments targeting leukocyte recruitment (fucoidin), TNF-α (infliximab), CXCL1 (antibody to CXCL1), IL-1 (IL-1ra), endothelin ETA (clazosentan) and ETB (BQ788) receptors and COX (indomethacin).Key Results: Carrageenin injection increased ST2 and IL-33 mRNA expression and IL-33 production in paw skin samples. Carrageenin-induced paw oedema, hyperalgesia and myeloperoxidase activity were reduced in ST2(-/-) compared with WT mice, effects mimicked by IL-33 injection in the paw. Furthermore, IL-33-induced hyperalgesia was reduced by fucoidin suggesting a role for recruited leukocytes in its hyperalgesic effect. IL-33-induced hyperalgesia in naïve mice was reduced by treatments targeting TNF, CXCL1, IL-1, endothelin receptors and COX while carrageenin-induced ST2-dependent TNF-α, CXCL1, IL-1β, IL-10 and PGE2 production and preproET-1 mRNA expression. Combining IL-33 and carrageenin at doses that were ineffective as single treatment induced significant hyperalgesia, oedema, myeloperoxidase activity and cytokine production in a ST2-dependent manner.Conclusions and Implications: IL-33/ST2 signalling triggers the production of inflammatory mediators contributing to carrageenin-induced inflammation. These data reinforces the importance of IL-33/ST2 signalling as a target in innate inflammation and inflammatory pain. [ABSTRACT FROM AUTHOR]

Aim To determine the prevalence of hyaline ring granulomas ( HRGs) in a large case series of inflammatory odontogenic cysts, and to investigate the nature of these structures. Methodology All records from the patients diagnosed with inflammatory odontogenic cysts between January 1970 and April 2009 were reviewed. Histologic sections were evaluated by light microscopy and cases with HRGs for which sufficient biological material was available were submitted to histochemical analysis ( Masson's trichrome) and immunohistochemistry ( CD34, CD68 and collagen IV). Results Twenty-two (3.3%) of the 661 cases of inflammatory odontogenic cysts diagnosed during the study period presented HRGs. The relative frequency of HRGs was higher amongst residual radicular cysts (6.1%), followed by paradental cysts (5.6%) and radicular cysts (3.0%). HRGs appeared as roughly circular homogeneous/fibrillar masses in 14 (63.6%) cases and as round structures enclosing amorphous material in 3 (13.6%) cases. Most (77.8%) roughly circular homogeneous/fibrillar masses were positive for collagen, whereas all (100.0%) round structures enclosing amorphous material were negative for this protein. Immunohistochemistry showed that most mononucleated cells and all multinucleated giant cells were positive for CD68, but negative for CD34, in all cases. In addition, collagen IV immunostaining was negative in amorphous structures and weakly positive in homogeneous/fibrillar masses. Conclusions The present results suggest a very low frequency of HRGs in inflammatory odontogenic cysts and support the hypothesis that these structures arise from the implantation of foreign material, most likely food particles of plant or vegetable origin. The diverse microscopic features of HRG possibly represent different developmental stages of this structure. [ABSTRACT FROM AUTHOR]

Major objectives of the poultry industry are to increase meat production and to reduce carcass fatness, mainly abdominal fat. Information on growth performance and carcass composition are important for the selection of leaner meat chickens. To enhance our understanding of the genetic architecture underlying the chemical composition of chicken carcasses, an F2 population developed from a broiler × layer cross was used to map quantitative trait loci (QTL) affecting protein, fat, water and ash contents in chicken carcasses. Two genetic models were applied in the QTL analysis: the line-cross and the half-sib models, both using the regression interval mapping method. Six significant and five suggestive QTL were mapped in the line-cross analysis, and four significant and six suggestive QTL were mapped in the half-sib analysis. A total of eleven QTL were mapped for fat (ether extract), five for protein, four for ash and one for water contents in the carcass using both analyses. No study to date has reported QTL for carcass chemical composition in chickens. Some QTL mapped here for carcass fat content match, as expected, QTL regions previously associated with abdominal fat in the same or in different populations, and novel QTL for protein, ash and water contents in the carcass are presented here. The results described here also reinforce the need for fine mapping and to perform multi-trait analyses to better understand the genetic architecture of these traits. [ABSTRACT FROM AUTHOR]

An F experimental population, developed from a broiler layer cross, was used in a genome scan of QTL for percentage of carcass, carcass parts, shank and head. Up to 649 F chickens from four paternal half-sib families were genotyped with 128 genetic markers covering 22 linkage groups. Total map length was 2630 cM, covering approximately 63% of the genome. QTL interval mapping using regression methods was applied to line-cross and half-sib models. Under the line-cross model, 12 genome-wide significant QTL and 17 suggestive linkages for percentages of carcass parts, shank and head were mapped to 13 linkage groups (GGA1, 2, 3, 4, 5, 7, 8, 9, 11, 12, 14, 18 and 27). Under the paternal half-sib model, six genome-wide significant QTL and 18 suggestive linkages for percentages of carcass parts, shank and head were detected on nine chicken linkage groups (GGA1, 2, 3, 4, 5, 12, 14, 15 and 27), seven of which seemed to corroborate positions revealed by the previous model. Overall, three novel QTL of importance to the broiler industry were mapped (one significant for shank% on GGA3 and two suggestive for carcass and breast percentages on GGA14 and drums and thighs percentage on GGA15). One novel QTL for wings% was mapped to GGA3, six novel QTL (GGA1, 3, 7, 8, 9 and 27) and suggestive linkages (GGA2, 4, and 5) were mapped for head%, and suggestive linkages were identified for back% on GGA2, 11 and 12. In addition, many of the QTL mapped in this study confirmed QTL previously reported in other populations. [ABSTRACT FROM AUTHOR]

An abstract of the study "Diabetes cardiomyopathy in diabetic patients without co-morbidities," by L. Mendes and colleagues, is presented.

We investigated the effects of Lutzomyia longipalpis salivary glands homogenate of wild-caught and laboratory-reared vectors on the lesion evolution and immunomodulation of the infection caused by Leishmania ( Leishmania) amazonensis. To compare the effect of both salivary glands homogenate (SGH), C57BL/6 mice were inoculated subcutaneously into the hind footpads or into the ear dermis with 106 promastigotes in the presence or not of SGH from wild-caught and laboratory-colonized sand flies. Comparing SGH groups, the lesion size was lower in mice co-inoculated with wild-caught SGH, as the parasitism and the infiltration of macrophages at the inoculation site. Wild-caught SGH also determined lower production of IL-4 and IL-10 but higher IL-12 levels compared with laboratory-reared SGH. Our findings address a probable bias by using SGH from laboratory-colonized sand flies instead of wild-caught vector SGH in studies concerning saliva effects. A possible mild influence of sand fly saliva in natural infections caused by Leishmania is also speculated, as infection is transmitted by wild and not by laboratory-reared vectors. [ABSTRACT FROM AUTHOR]

An F2 population established by crossing a broiler male line and a layer line was used to map quantitative trait loci (QTL) affecting abdominal fat weight, abdominal fat percentage and serum cholesterol and triglyceride concentrations. Two genetic models, the line-cross and the half-sib, were applied in the QTL analysis, both using the regression interval method. Three significant QTL and four suggestive QTL were mapped in the line-cross analysis and four significant and four suggestive QTL were mapped in the half-sib analysis. A total of five QTL were mapped for abdominal fat weight, six for abdominal fat percentage and four for triglyceride concentration in both analyses. New QTL associated with serum triglyceride concentration were mapped on GGA5, GGA23 and GG27. QTL mapped between markers LEI0029 and ADL0371 on GGA3 for abdominal fat percentage and abdominal fat weight and a suggestive QTL on GGA12 for abdominal fat percentage showed significant parent-of-origin effects. Some QTL mapped here match QTL regions mapped in previous studies using different populations, suggesting good candidate regions for fine-mapping and candidate gene searches. [ABSTRACT FROM AUTHOR]

An F2 resource population, derived from a broiler × layer cross, was used to map quantitative trait loci (QTL) for body weights at days 1, 35 and 41, weight gain, feed intake, feed efficiency from 35 to 41 days and intestinal length. Up to 577 F2 chickens were genotyped with 103 genetic markers covering 21 linkage groups. A preliminary QTL mapping report using this same population focused exclusively on GGA1. Regression methods were applied to line-cross and half-sib models for QTL interval mapping. Under the line-cross model, eight QTL were detected for body weight at 35 days (GGA2, 3 and 4), body weight at 41 days (GGA2, 3, 4 and 10) and intestine length (GGA4). Under the half-sib model, using sire as common parent, five QTL were detected for body weight at day 1 (GGA3 and 18), body weight at 35 days (GGA2 and 3) and body weight at 41 days (GGA3). When dam was used as common parent, seven QTL were mapped for body weight at day 1 (GGA2), body weight at day 35 (GGA2, 3 and 4) and body weight at day 41 (GGA2, 3 and 4). Growth differences in chicken lines appear to be controlled by a chronological change in a limited number of chromosomal regions. [ABSTRACT FROM AUTHOR]

The article assesses the reliability of the linear measurement of mid-thigh soft-tissue thickness (STT) in the late third trimester citing the derivation of a formula for the estimation of fetal weight (EFW). The results confirm the potential of the linear measurement of mid-thigh STT as a valuable parameter for the sonographic assessment of fetal growth and EFW.

Aim To determine whether systolic and diastolic blood pressure (BP) means, during ambulatory BP monitoring (ABPM), are more strongly correlated with microvascular complications and echocardiographic structural alterations than night-time/daytime (N/D) BP ratio. Methods A cross-sectional study was conducted in 270 Type 2 diabetes mellitus (DM) outpatients who underwent clinical and laboratory investigations, urinary albumin excretion rate (UAER) determination, echocardiography, office and 24-h ABPM (Spacelabs 90207). Results UAER, after multivariate adjustments, was associated with office BP (systolic: R2a 0.162, P < 0.001; diastolic: R2a 0.124, P < 0.001) and ABPM (24-h systolic: R2a 0.195, P < 0.001; 24-h diastolic: R2a 0.197, P < 0.001) but not with N/D BP ratios (systolic: R2a 0.062, P = 0.080; diastolic: R2a 0.063, P = 0.069). Similar results were observed for echocardiographic parameters. The presence of retinopathy was associated only with night-time BP values [systolic means: odds ratio (OR) 1.13, 95% confidence interval (CI) 1.03–1.24 and diastolic means: OR 1.21, CI 1.04–1.40 and N/D diastolic BP ratio > 0.90, OR 3.21, CI 1.65–6.25]. Conclusions UAER and echocardiographic structural alterations had more consistent correlations of a greater magnitude with systolic BP means than with N/D BP ratios. The nocturnal BP values appear to be more relevant for diabetic retinopathy. BP measurement in patients with Type 2 DM should take into account the 24-h period rather than focusing on a specific time span of BP homeostasis. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy is considered to be a neurovascular disease. But in fact, retinal neurodegeneration is present before any microcirculatory abnormalities can be detected in ophthalmoscopic examination. We know this from functional studies documenting electroretinogram abnormalities, loss of dark adaptation, contrast sensitivity and color vision and abnormal microperimetry occur before any vascular abnormality is detected. Novel imaging devices have allowed this pre-vascular damage to be quantified in a non-invasive and reproducible way using spectral domain optical coherence tomography ( SD- OCT) that allows in vivo retinal layer thickness measurement. The extent to which this new technology can be used in the clinical setting for early screening in diabetic retinopathy will be the focus of this lecture. The review of the state of the art in this exciting new field of study may prove valuable in the management of this condition. [ABSTRACT FROM AUTHOR]

Purpose To evaluate choroidal thickness (CT) in diabetic patients without diabetic retinopathy (DR) using enhanced depth imaging spectral-domain optical coherence tomography (EDI SD- OCT). To correlate CT with disease duration, systemic blood pressure (BP), glycemia, intraocular pressure (IOP) and ocular pulse amplitude (OPA). Methods Prospective, observational case-control study. A complete ophthalmological examination was performed (visual acuity, refraction, Goldmann applanation and dynamic contour tonometries, fundoscopy and axial length). CT was assessed by a non-invasive procedure using an EDI- OCT (Spectralis Heidelberg) at 13 locations (subfoveal and 3 measurements 500 μm apart in all 4 directions - nasal, temporal, superior and inferior). Results 180 patients were recruited: 130 diabetic patients with no DR and 50 healthy controls; one eye per patient included in the study. CT at 1500 μm above the fovea was significantly thicker in the diabetic group (239.9 ± 56 μm vs 268.2 ± 67.7 μm, p = 0.001). None of the other topographic region comparisons were statistically different (p > 0.05). In diabetic patients CT was not correlated with disease duration, BP, glycemia or IOP. CT was positively correlated with OPA in 12 points in diabetic patients (r between 0.19 and 0.27, p < 0.05) but not in the control group. CT variation coefficients in the diabetic group were statistically lower than in the control group (p < 0.01). Conclusions The thickening of the choroid at 1500 μm superior of the fovea in diabetic patients without DR may correspond to the diabetic choroidopathy in mid-periphery presented before DR. Moreover, this tissue may be functionally different, as the pattern of correlations seems to differ between groups. Further studies are needed to explore these differences and the potential of the CT in the clinical setting. [ABSTRACT FROM AUTHOR]

Purpose The authors intend to present an analysis and comparison of the choroidal thickness in more distant superior regions. Choroidal thickness is increased in a heterogeneous pattern superiorly to the fovea in diabetic patients without diabetic retinopathy. Methods Observational case-control study of 60 eyes of 60 patients with diabetes mellitus type 2 without diabetic retinopathy. A control group of 31 eyes of 31 patients without diabetes with similar demographic features was also created. All the patients were recruited from the same outpatient clinic. Enhanced depth imaging spectral-domain optical coherence tomography (EDI SD- OCT SPECTRALIS®) was performed and high-resolution macular scans were obtained. Choroidal thickness was evaluated 2000 μm superiorly to the fovea by manual layer segmentation. Previous studies have validated the validity of using a manual layer segmentation procedure in OCT. Statistical analysis was done with SPSS Statistics. A p value <0.05 was considered statistically significant. Results Diabetic patients were in average 67.0 ± 9.6 years old and 56.7% were male. Average choroidal thickness 2000 μm superiorly to the fovea was 287.77 ± 74.32 μm in diabetic patients and 249.81 ± 53.96 μm in non-diabetic patients. There was a significant increase in choroidal thickness in diabetic patients when compared to non-diabetic patients (T-student, p = 0.014). Conclusions Choroidal thickness can be accurately measured using high-definition macular OCT scans. This study documented structural differences in the choroid associated with diabetes mellitus type 2 that are not only present in the central foveal area as reported in previous studies. Diabetes Mellitus is associated with multiple microvascular dysfunctions that are probably coupled with choroidal vascular modifications that induce changes in thickness. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the difference in assessment between fundoscopic and confocal scanning vertical cup-disc-ratio (VCDR) in open angle glaucoma patients. Methods Data from a single eye of normal tension (NTG) and primary open angle glaucoma (POAG) patients from the Leuven Eye Study were included: age, gender, visual field mean deviation (MD), fundoscopic and HRT III VCDR assessment as well as mean retinal nerve fiber layer thickness (mRNFL). Differences within groups were assessed by paired sample t-tests. Receiver operator curves (ROC) were constructed to assess and compute the likelihood ratio and positive predictive value. Results 303 eyes (161 POAG and 142 NTG) were included. The average VCDR clinically assessed was significantly larger than the value derived from the HRT III software (0.81 ± 0.14 versus 0.61 ± 0.16, p < 0.001) and this difference remained statistically significant in both groups. In advanced glaucoma (MD > −12 dB), the area under the curve for HRT III and fundoscopic VCDR was respectively 0.80 ± 0.05 versus 0.84 ± 0.04 for NTG and 0.66 ± 0.044 versus 0.82 ± 0.033 for POAG. To predict a MD of maximum -12 dB with 80% certainty in NTG patients the VCDR needs to be at least 0.79 and 0.88 for HRT III and fundoscopic VCDR values, whereas in POAG patients these numbers are 0.88 and 0.93, respectively. Conclusions Clinical assessment of VCDR renders significantly higher values than HRT III derived values. Fundoscopic assessment of the optic nerve can predict better the visual field damage compared to the HRT III assessment. [ABSTRACT FROM AUTHOR]

Purpose To investigate the association between anterior lamina cribrosa depth (ALCD) determined with enhanced depth imaging spectral-domain optical coherence tomography (EDI- OCT) and IOP in a healthy Portuguese population. Methods Prospective observational study conducted between January and April 2015 of 44 subjects with a irrelevant ophthalmologic history. EDI- OCT of optic nerve head (ONH) was performed in all participants (2 cross scans: vertical and horizontal). ALCD was defined as the perpendicular distance between the line connecting both edges of Bruch's membrane and the anterior border of the lamina cribrosa, at the maximum depth point. An experienced operator manually segmented ALCD and a mean of the two consecutive blinded measurements was computed. To guarantee observations' independence, only one eye was considered per subject. Only high-quality images were accepted. The tenets of the Declaration of Helsinki were followed. Statistical analyses were performed using STATA 13.0. Results Studied population included 44 subjects (26 women), with a mean age of 62.9 ± 14.3 years. Mean vertical and horizontal maximum ALCD was 453.3 ± 88 μm and 436.1 ± 78.7 μm, respectively. Neither gender nor age were associated with these ALCD scans (p > 0.05). When controlling for gender, age and spherical equivalent, maximum vertical and horizontal ALCD increased, respectively, by 8.8 μm (95% confidence interval [ CI], 0.6-17.0 μm; p = 0.04) and 8.1 μm (95% CI, 0.4-15.7 μm; p = 0.04) per mmHg increase in IOP. Conclusions Our sample of healthy subjects presented a statistically significant positive linear relation between IOP and ALCD, when controlling for possible confounding factors. Our results may trigger furthers studies to better elucidate the role of IOP in morphological and functional dynamics of the ONH. [ABSTRACT FROM AUTHOR]

Purpose To determine intra and inter-rater agreement of anterior lamina cribrosa depth (ALCD) manual measurements using enhanced depth imaging spectral-domain optical coherence tomography (EDI- OCT). Methods Double blind prospective observational study between December 14 and May 15. EDI- OCT of optic nerve head was performed in subjects with an irrelevant ophthalmologic history (2 cross scans: vertical and horizontal). ALCD was defined as the perpendicular distance between the line connecting both edges of Bruch's membrane and the anterior border of the lamina cribrosa, at the maximum depth point. Two double-blinded experienced operators manually measured ALCD twice, with a one-month interval. Intra and inter-rater agreement was evaluated using intraclass correlation coefficients (ICC), concordance correlation coefficients (CCC) and Bland-Altman (BA) plots for the right eye vertical (RV) and horizontal (RH) scans and left eye vertical (LV) and horizontal (LH) scans. Statistical analyses were performed using STATA 13.0. Results Studied population included 44 subjects (26 women), with a mean age of 62.9 ± 14.3 years. Mean vertical and horizontal maximum ALCD was 453.3 ± 88 μm and 436.1 ± 78.7 μm, respectively. Intra-rater ICC for ALCD in RV, RH, LV and LH were 0.98, 0.94, 0.97 and 0.96, respectively. Inter-rater ICC for ALCD in RV, RH, LV and LH were all 0.99. Intra-rater CCC for ALCD in RV, RH, LV and LH were 0.98, 0.93, 0.97 and 0.96. Inter-rater CCC for ALCD in RV, RH, LV and LH were all 0.99. Bland-Altman plots suggested that almost all observations were within the 95% limits of agreement. Conclusions ALCD manual measurements with EDI- OCT showed high agreement among intra and inter-rater measurements in healthy eyes. EDI- OCT is a reliable tool for ALCD measurement, which can provide potentially useful information for integrated glaucoma management. [ABSTRACT FROM AUTHOR]

Purpose To present a comparison of the thickness variation of the different retinal layers in diabetic patients without diabetic retinopathy. Methods A prospective observational study was performed. 175 eyes of 175 patients: 125 diabetic patients without diabetic retinopathy and 50 subjects without diabetes (age and gender matched) from the ophthalmology outpatient clinic were included. Optical Coherence Tomography (OCT SPECTRALIS®) was performed with high-resolution macular scans. Automated retinal layer segmentation was performed using validated software and layers thicknesses were determined. The coefficient of variation of the different layers was calculated. A p value < 0.05 was considered statistically significant. Results Diabetic patients were in average 66.9 ± 9.3 years old. There weren't significant differences in the coefficients of variation between diabetic and non-diabetic patients: total retinal thickness (9.3% vs. 9.3%; p = 0.39), RNFL (41.09% vs. 42.25%; p = 0.33), GCL (30.39% vs. 31.13%; p = 0.20), IPL (23.62% vs. 24.13; p = 0.40), ILN (21.26% vs. 19.86; p = 0.44). Conclusions Previous studies have demonstrated that choroidal thickness coefficient of variation is lower in diabetic patients. Nevertheless, in retinal layers no difference was found in diabetic patients without macular edema. There is a combination of choroid with diminished thickness coefficient of variation and retinal layers with normal thickness coefficient of variation. This suggests that vascular choroidal pathology precedes retinal layers dysfunction. Exudation and lipid accumulation associated with microvascular retinal dysfunction and changes in axonal homeostasis only appear at a second step. This study emphasizes the importance of the retinal layer thickness measurement with OCT in the evaluation of diabetic patients. [ABSTRACT FROM AUTHOR]

Purpose To evaluate retinal layers thickness in diabetic patients without diabetic retinopathy (DR) using spectral-domain optical coherence tomography (SD- OCT). To correlate retinal layers thickness in diabetic patients with disease duration, systemic blood pressure ( BP), glycemia, glycosylate haemoglobin (HbA1c), intraocular pressure (IOP) and ocular pulse amplitude (OPA). Methods Prospective, observational case-control study. A total of 175 eyes from 175 patients (125 diabetic patients without DR; 50 healthy controls) were recruited from the outpatient clinic in a tertiary center. A complete ophthalmological examination was performed (visual acuity, refraction, Goldmann applanation and dynamic contour tonometries, fundoscopy, axial length and SD- OCT-Spectralis®). After automated retinal segmentation the thickness of each layer was calculated in the 9 ETDRS areas. Results A significant increase of retinal nerve fiber layer (RNFL) thickness in inner and outer rings was found in diabetic eyes vs. controls (p between <0.0001 and 0.02). Thickness was also increased in specific sites of ganglion cell layer (GCL), inner nuclear layer (INL) and retinal pigment epithelium (RPE) in diabetic eyes (p between 0.001 and 0.03). A significant decrease of outer plexiform layer (OPL) was detected in diabetic eyes at two sites of the inner ring (p = 0.04 and p < 0.0001). The different retinal layers weren't correlated with systemic BP, glycemia, HbA1c, IOP and OPA, but the photoreceptor layer was negatively correlated with disease duration at 3 sites (r between −0.18 and −0.21, p < 0.05). Conclusions In diabetic patients without DR thickness of the inner retina seems to be increased. This suggests that metabolic and morphological changes of the cells of these inner retinal layers occur early and before the apoptosis and neural degeneration. [ABSTRACT FROM AUTHOR]

Purpose Nanomedicine has been receiving greater attention in recent years due to the ability to use materials and devices at the size of intracellular structures and molecules, involving systems in the order of <100 nm. In particular, nanosized materials can provide substantial advantages when compared to current therapeutics that are used in the treatment of ocular diseases. Nanotechnology-based approaches are being explored in order to enhance drug permeation, to control mechanisms of drug release and to improve the action of nanocarriers with specific targeting moieties. From biopharmaceuticals to continuous intraocular pressure biosensors and tissue regeneration, nanotechnology provides an impressive range of possibilities to explore and improve patient care. Methods Herein, we review the most recent literature regarding nanotechnology applications in ophthalmology, highlighting their advantages and challenges to overcome, prospecting them in terms of clinical utility. Results Nanocarriers, nanodevices and nanostructured biocoatings with applications in the treatment of ocular diseases are resumed and their impact in the evolution of ophthalmology is discussed. We present a recent study about nanostructured films composed of drugs encapsulated in nanocarriers with applications in glaucoma treatment. Our results suggest that nanocarriers improve drug delivery and that specific drug amounts can be released during controlled periods of time. Conclusions Our research emphasizes new trends and applications of nanodevices in ophthalmology. Nanomedicine is definitely part of a paradigm shift in healthcare providing, making it possible to reach excellence in ophthalmological diagnosis and therapeutics. Acknowledgements The authors thank FCT-Portugal for financial support under the project UID/ EEA/50008/2013 and Post-Doc grant to QF. [ABSTRACT FROM AUTHOR]

Purpose Plateau iris configuration (PIC) is a rare condition involving an angle closure unrelated to pupillary block. It may be defined by a narrow angle and a double-hump configuration on gonioscopy. Plateau iris syndrome (PIS) may lead to acute angle-closure glaucoma due to an anterior displacement and rotation of the ciliary body. It has been proposed that ultrasound biomicroscopy (UBM) is helpful in PIC/ PIS diagnosis. Our work aims to describe UBM quantitative and qualitative findings in patients whose gonioscopy suggested a PIC/ PIS Methods Cross-sectional study involving patients with a double hump gonioscopic finding. UBM was then performed by a blinded observer and evaluated for the presence of following ultrasonographic (US) criteria: (1) a thick and flat iris, (2) a sharp, square root angulation on its insertion, (3) an anterior rotation of the ciliary body, (4) irido-ciliary sulcus narrowing, (5) iris-trabecular apposition and (6) a relatively normal anterior chamber (AC) depth. Only high-quality images were accepted Results From September 14 to May 15, 35 patients (59 eyes) were recruited. Only 3 eyes presented the six US criteria, 23 eyes filled five of the criteria, 13 satisfied four criteria, 16 presented three criteria and 4 two criteria. The most commonly verified criteria (over 95% of them) were a thick and flat iris and a square root insertion. There was no association between any of these criteria and sex nor age (p > 0.10). Furthermore, the presence/absence of these criteria did not correlate with either anterior chamber depth, lens vault and lens length (p > 0.10) Conclusions The majority of patients presenting with clinical iris plateau syndrome do not fulfill the entire US criteria for this condition. However, the US-based iris morphological parameters seem to be present in nearly all iris plateau patients. [ABSTRACT FROM AUTHOR]

Purpose Plateau iris configuration (PIC) is a rare condition involving an angle closure unrelated to pupillary block. It may be defined by a narrow angle and a double-hump configuration on gonioscopy. Plateau iris syndrome (PIS) may lead to acute angle-closure glaucoma due to an anterior displacement and rotation of the ciliary body. It has been proposed that ultrasound biomicroscopy (UBM) is helpful in PIC/ PIS diagnosis. Our work aims to describe UBM quantitative and qualitative findings in patients whose gonioscopy suggested a PIC/ PIS. Methods Cross-sectional study involving patients with a double hump gonioscopic finding. UBM was then performed by a blinded observer and evaluated for the presence of following ultrasonographic (US) criteria: 1) a thick and flat iris, 2) a sharp, square root angulation on its insertion, 3) an anterior rotation of the ciliary body, 4) irido-ciliary sulcus narrowing, 5) iris-trabecular apposition and 6) a relatively normal anterior chamber (AC) depth. Only high-quality images were accepted. Results From Sep/14-May/15, 35 patients (59 eyes) were recruited. Only 3 eyes presented the six US criteria, 23 eyes filled five of the criteria, 13 satisfied four criteria, 16 presented three criteria and 4 two criteria. The most commonly verified criteria (over 95% of them) were a thick and flat iris and a square root insertion. There was no association between any of these criteria and sex nor age (p > 0.10). Furthermore, the presence/absence of these criteria did not correlate with either anterior chamber depth, lens vault and lens length (p > 0.10). Conclusions The majority of patients presenting with clinical iris plateau syndrome do not fulfill the entire US criteria for this condition. However, the US-based iris morphological parameters seem to be present in nearly all iris plateau patients. [ABSTRACT FROM AUTHOR]