Age-Related Macular Degeneration and Extramacular Drusen: Genetic Associations in the Coimbra Eye Study.

Purpose: To explore the association between the genetics of age-related macular degeneration (AMD) and extramacular drusen (EMD) in patients with and without AMD. Methods: We included 1753 eyes (912 subjects) with phenotypic characterization regarding AMD and EMD. Genetic sequencing and the genetic risk score (GRS) for AMD were performed according to the EYE-RISK consortium methodology. To test for differences in the GRS from EMD cases, AMD cases, and controls, a clustered Wilcoxon rank-sum test was used. The association of AMD, EMD, and the GRS was evaluated using logistic regression models adjusted for age and sex. Individual associations of common risk variants for AMD with EMD were explored. Results: EMD were found in 755 eyes: 252 (14.4%) with AMD and 503 (28.7%) without. In total, 122 eyes (7.0%) had only AMD, and 876 (50.0%) were controls. EMD were strongly associated with AMD (odds ratio [OR], 3.333; 95% confidence interval [CI], 2.356-4.623; P < 0.001). The GRS was associated with an increased risk of AMD (OR, 1.416; 95% CI, 1.218-1.646; P < 0.001) but not with EMD. Individually, the common risk variants ARMS2 rs10490924 (P = 0.042), C3 rs2230199 (P = 0.042), and CETP rs5817082 (P = 0.042) were associated with EMD, after adjustment for AMD, sex, and age. Conclusions: We found a strong association between EMD and AMD, suggesting a common pathogenesis. The GRS for AMD was not associated with EMD, but a partially overlapping genetic basis was suggested when assessing individual risk variants. We propose that EMD per se do not represent an increase in the global genetic risk for AMD.

Interaction between genetics and the adherence to the Mediterranean diet: the risk for age-related macular degeneration. Coimbra Eye Study Report 8.

BACKGROUND: Age-related macular degeneration (AMD) is a multifactorial degenerative disease of the macula. Different factors, environmental, genetic and lifestyle, contribute to its onset and progression. However, how they interconnect to promote the disease, or its progression, is still unclear. With this work, we aim to assess the interaction of the genetic risk for AMD and the adherence to the Mediterranean diet in the Coimbra Eye Study. METHODS: Enrolled subjects (n = 612) underwent ophthalmological exams and answered a food questionnaire. Adherence to the Mediterranean diet was assessed with mediSCORE. An overall value was calculated for each participant, ranging from 0 to 9, using the sum of 9 food groups, and a cut off value of ≥ 6 was considered high adherence. Rotterdam Classification was used for grading. Participants' genotyping was performed in collaboration with The European Eye Epidemiology Consortium. The genetic risk score (GRS) was calculated for each participant considering the number of alleles at each variant and their effect size. Interaction was assessed with additive and multiplicative models, adjusted for age, sex, physical exercise, and smoking. RESULTS: The AMD risk was reduced by 60% in subjects with high adherence to the Mediterranean diet compared to subjects with low adherence to the Mediterranean diet. Combined effects of having low adherence to the Mediterranean diet and high GRS led to almost a 5-fold increase in the risk for AMD, compared to low GRS and high adherence to the Mediterranean diet. The multiplicative scale suggested a multiplicative interaction, although not statistically significant [odds ratio (OR) = 1.111, 95% CI 0.346-3.569, P = 0.859]. The additive model showed a causal positive effect of the interaction of GRS and adherence to the Mediterranean diet: relative excess risk due to interaction (RERI) = 150.9%, (95% CI: - 0.414 to 3.432, P = 0.062), attributable proportion due to interaction (AP) = 0.326 (95% CI: - 0.074 to 0.726, P = 0.055) and synergy index (SI) = 1.713 (95% CI: 0.098-3.329, P = 0.019). High GRS people benefited from adhering to the Mediterranean diet with a 60% risk reduction. For low-GRS subjects, a risk reduction was also seen, but not significantly. CONCLUSIONS: Genetics and Mediterranean diet interact to protect against AMD, proving there is an interplay between genetics and environmental factors. TRIAL REGISTRATION: The AMD Incidence (NCT02748824) and Lifestyle and Food Habits Questionnaire in the Portuguese Population Aged 55 or More (NCT01715870) studies are registered at www. CLINICALTRIALS: gov . Five-year Incidence of Age-related Macular Degeneration in the Central Region of Portugal (AMD IncidencePT); NCT02748824: date of registration: 22/04/16. Lifestyle and Food Habits Questionnaire in the Portuguese Population Aged 55 or More; NCT01715870: date of registration: 29/10/12.

Association of Systemic Medication Use with Glaucoma and Intraocular Pressure: The European Eye Epidemiology Consortium.

PURPOSE: To investigate the association of commonly used systemic medications with glaucoma and intraocular pressure (IOP) in the European population. DESIGN: Meta-analysis of 11 population-based cohort studies of the European Eye Epidemiology Consortium. PARTICIPANTS: The glaucoma analyses included 143 240 participants and the IOP analyses included 47 177 participants. METHODS: We examined associations of 4 categories of systemic medications-antihypertensive medications (ß-blockers, diuretics, calcium channel blockers [CCBs], α-agonists, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers), lipid-lowering medications, antidepressants, and antidiabetic medications-with glaucoma prevalence and IOP. Glaucoma ascertainment and IOP measurement method were according to individual study protocols. Results of multivariable regression analyses of each study were pooled using random effects meta-analyses. Associations with antidiabetic medications were examined in participants with diabetes only. MAIN OUTCOME MEASURES: Glaucoma prevalence and IOP. RESULTS: In the meta-analyses of our maximally adjusted multivariable models, use of CCBs was associated with a higher prevalence of glaucoma (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.08 to 1.39). This association was stronger for monotherapy of CCBs with direct cardiac effects (OR, 1.96; 95% CI, 1.23 to 3.12). No other antihypertensive medications, lipid-lowering medications, antidepressants, or antidiabetic medications were associated with glaucoma. Use of systemic ß-blockers was associated with a lower IOP (ß coefficient, -0.33 mmHg; 95% CI, -0.57 to -0.08 mmHg). Monotherapy of both selective systemic ß-blockers (ß coefficient, -0.45 mmHg; 95% CI -0.74 to -0.16 mmHg) and nonselective systemic ß-blockers (ß coefficient, -0.54 mmHg; 95% CI, -0.94 to -0.15 mmHg) was associated with lower IOP. A suggestive association was found between use of high-ceiling diuretics and lower IOP (ß coefficient, -0.30 mmHg; 95% CI, -0.47 to -0.14 mmHg) but not when used as monotherapy. No other antihypertensive medications, lipid-lowering medications, antidepressants, or antidiabetic medications were associated with IOP. CONCLUSIONS: We identified a potentially harmful association between use of CCBs and glaucoma prevalence. Additionally, we observed and quantified the association of lower IOP with systemic ß-blocker use. Both findings potentially are important, given that patients with glaucoma frequently use systemic antihypertensive medications. Determining causality of the CCB association should be a research priority. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Association of lipid-lowering drugs and antidiabetic drugs with age-related macular degeneration: a meta-analysis in Europeans.

BACKGROUND/AIMS: To investigate the association of commonly used systemic medications with prevalent age-related macular degeneration (AMD) in the general population. METHODS: We included 38 694 adults from 14 population-based and hospital-based studies from the European Eye Epidemiology consortium. We examined associations between the use of systemic medications and any prevalent AMD as well as any late AMD using multivariable logistic regression modelling per study and pooled results using random effects meta-analysis. RESULTS: Between studies, mean age ranged from 61.5±7.1 to 82.6±3.8 years and prevalence ranged from 12.1% to 64.5% and from 0.5% to 35.5% for any and late AMD, respectively. In the meta-analysis of fully adjusted multivariable models, lipid-lowering drugs (LLD) and antidiabetic drugs were associated with lower prevalent any AMD (OR 0.85, 95% CI=0.79 to 0.91 and OR 0.78, 95% CI=0.66 to 0.91). We found no association with late AMD or with any other medication. CONCLUSION: Our study indicates a potential beneficial effect of LLD and antidiabetic drug use on prevalence of AMD across multiple European cohorts. Our findings support the importance of metabolic processes in the multifactorial aetiology of AMD.

Common and rare genetic risk variants in age-related macular degeneration and genetic risk score in the Coimbra eye study.

PURPOSE: To determine the contribution of common and rare genetic variants in age-related macular degeneration (AMD) in a Portuguese population from the Coimbra Eye Study (CES), and the genetic risk score (GRS). METHODS: Participants underwent ophthalmologic examination and imaging. A centralized reading centre performed AMD staging. Genetic sequencing was carried out with the EYE-RISK assay. Sixty-nine single nucleotide polymorphisms (SNPs) were genotyped and tested for association with AMD. Case-control and progression-to-AMD analyses were performed using logistic regression to assess allelic odds ratio (OR) at a 95% confidence interval (CI) for each variant. GRS was calculated for cases/controls and progressors/non-progressors. Cumulative impact of rare variants was compared between cases/controls using logistic regression. RESULTS: In case-control analysis (237 cases/640 controls) variants associated with risk of disease were: ARMS2 rs10490924, ARMS2_HTRA1 rs3750846, CFH rs35292876, SLC16A8 rs8135665, TGFBR1 rs1626340. Major risk variants ARMS2/HTRA1 rs3750846, CFH rs570618 and C3 rs2230199 had unexpected lower allele frequency (AF), and the highest risk-conferring variant was a rare variant, CFH rs35292876 (OR, 2.668; p-value = 0.021). In progression-to-AMD analysis (137 progressors/630 non-progressors), variants associated with risk of progression were ARMS2 rs10490924, ARMS2_HTRA1 rs3750846, CFH rs35292876. GRS of cases/controls was 1.124 ± 1.187 and 0.645 ± 1.124 (p-value < 0.001), and of progressors/non-progressors was 1.190 ± 1.178 and 0.669 ± 1.141 (p-value < 0.001). Higher proportion of pathogenic rare CFH variants was observed in cases (OR, 9.661; p-value < 0.001). CONCLUSIONS: Both common and rare variants were associated with AMD, but a CFH rare variant conferred the highest risk of disease while three major risk variants had a lower-than-expected AF in our population originary from a geographic region with lower prevalence of AMD. GRS was still significantly higher in AMD patients. Damaging CFH rare variants were cumulatively more common in AMD cases.

Naphthalene Detection in Air by Highly Sensitive TiO2 Sensor: Real Time Response to Concentration Changes Monitored by Simultaneous UV Spectrophotometry.

Volatile low-weight polycyclic aromatic hydrocarbons (PAHs) are known to be potentially toxic to humans and animals. Their detection in ambient air has been of great interest in recent years and various detection methods have been implemented. In this study, we used naphthalene as a basic model of such compounds and constructed our own version of a titanium oxide-based sensor system for its detection. The main goal of the study was to clearly demonstrate the effectiveness of this type of sensor, record its response under well-controlled conditions, and compare that response to concentration measurements made by the widely accepted spectrophotometric method. With that goal in mind, we recorded the sensor response while monitoring naphthalene vapor concentrations down to 95 nM as measured by spectrophotometry. Air flow over the sensor was passed continuously and sample measurements were made every 3 min for a period of up to 2 h. Over that period, several cycles of naphthalene contamination and cleaning were implemented and measurements were recorded. The relative humidity and temperature of the air being sampled were also monitored to assure no major variations occurred that could affect the measurements. The sensor showed high sensitivity and a reproducible response pattern to changes in naphthalene concentration. It could be easily "cleaned" of the compound in ten minutes by means of the application of UV light and the passing of fresh air. Pending testing with other volatile PAH, this type of sensor proves to be an effective and inexpensive way to detect naphthalene in air.

Phenotypic Expression of CFH Rare Variants in Age-Related Macular Degeneration Patients in the Coimbra Eye Study.

Purpose: To determine the association between rare genetic variants in complement factor H (CFH) and phenotypic features in age-related macular degeneration (AMD) patients from the Coimbra Eye Study (CES). Methods: AMD patients from the Incidence CES (NCT02748824) underwent ophthalmologic examination and color fundus photography, spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence, and near-infrared imaging. Multimodal phenotypic characterization was carried out in a centralized reading center. The coding and splice-site regions of the CFH gene were sequenced through single-molecule molecular inversion probe-based next-generation sequencing in association with the EYE-RISK consortium. Variants with minor allele frequency <0.05 resulting in splice-site or protein change were selected. Differences in phenotypic features between carriers and noncarriers were analyzed using generalized estimated equations logistic regression models, considering intereye correlations. Results: We included 39 eyes of 23 patients carrying rare CFH variants and 284 eyes of 188 noncarriers. Carrier status was associated with having higher drusen burden in the macula in the inner Early Treatment Diabetic Retinopathy Study circle (odds ratio [OR], 5.44 [95% confidence interval {CI}, 1.61-18.37]; P = 0.006), outer circle (OR, 4.37 [95% CI, 1.07-17.77]; P = 0.04), and full grid (OR, 4.82 [95% CI, 1.13-20.52]; P = 0.033). In SD-OCT, a lower total macular volume and lower inner retinal layers' volume (OR, 0.449 [95% CI, 0.226-0.894]; P = 0.023; OR, 0.496 [95% CI, 0.252-0.979]; P = 0.043) and pigment epithelial detachments (PEDs) (OR, 5.24 [95% CI, 1.08-25.44]; P = 0.04) were associated with carrying a rare CFH variant. Carriers with subretinal drusenoid deposits (SDD) had the rare variant P258L in all cases except one. Conclusions: We identified in our cohort phenotypic differences between carriers and noncarriers of rare variants in the CFH gene. Carriers had more severe disease, namely superior drusen burden, PEDs, and thinner retinas. The rare variant P258L may be associated with SDD. Carriers are probably at increased risk of progression.

Putative Biomarkers in Tears for Diabetic Retinopathy Diagnosis.

Purpose: Tear fluid biomarkers may offer a non-invasive strategy for detecting diabetic patients with increased risk of developing diabetic retinopathy (DR) or increased disease progression, thus helping both improving diagnostic accuracy and understanding the pathophysiology of the disease. Here, we assessed the tear fluid of nondiabetic individuals, diabetic patients with no DR, and diabetic patients with nonproliferative DR (NPDR) or with proliferative DR (PDR) to find putative biomarkers for the diagnosis and staging of DR. Methods: Tear fluid samples were collected using Schirmer test strips from a cohort with 12 controls and 54 Type 2 Diabetes (T2D) patients, and then analyzed using mass spectrometry (MS)-based shotgun proteomics and bead-based multiplex assay. Tear fluid-derived small extracellular vesicles (EVs) were analyzed by transmission electron microscopy, Western Blotting, and nano tracking. Results: Proteomics analysis revealed that among the 682 reliably quantified proteins in tear fluid, 42 and 26 were differentially expressed in NPDR and PDR, respectively, comparing to the control group. Data are available via ProteomeXchange with identifier PXD033101. By multicomparison analyses, we also found significant changes in 32 proteins. Gene ontology (GO) annotations showed that most of these proteins are associated with oxidative stress and small EVs. Indeed, we also found that tear fluid is particularly enriched in small EVs. T2D patients with NPDR have higher IL-2/-5/-18, TNF, MMP-2/-3/-9 concentrations than the controls. In the PDR group, IL-5/-18 and MMP-3/-9 concentrations were significantly higher, whereas IL-13 was lower, compared to the controls. Conclusions: Overall, the results show alterations in tear fluid proteins profile in diabetic patients with retinopathy. Promising candidate biomarkers identified need to be validated in a large sample cohort.

Estado e transição na tradição marxista: formas políticas para pensar a atualidade / State and transition in the marxist tradition: political forms to think about the present

Resumo: Buscou-se a concepção de Estado e sua alternativa na tradição marxista para uma reflexão das possibilidades de transformação da realidade atual conjuntamente com a teoria da transição de Mészáros, já que apesar do progresso econômico persiste o subdesenvolvimento social. Conclui-se que a democratização da forma política atual é um caminho para a transformação e que a crise proporciona uma janela de oportunidades para novas concepções políticas.

Abstract: The concept of State and its alternative in the Marxist tradition were sought to reflect on the possibilities of transforming the current reality together with Mészáros' theory of transition, since despite economic progress, social underdevelopment persists. It is concluded that the democratization of the current political form is a path to transformation, and that the crisis provides a window of opportunity for new political conceptions.

Urinary Mass Spectrometry Profiles in Age-Related Macular Degeneration.

We and others have shown that patients with different severity stages of age-related macular degeneration (AMD) have distinct plasma metabolomic profiles compared to controls. Urine is a biofluid that can be obtained non-invasively and, in other fields, urine metabolomics has been proposed as a feasible alternative to plasma biomarkers. However, no studies have applied urinary mass spectrometry (MS) metabolomics to AMD. This study aimed to assess urinary metabolomic profiles of patients with different stages of AMD and a control group. We included two prospectively designed, multicenter, cross-sectional study cohorts: Boston, US (n = 185) and Coimbra, Portugal (n = 299). We collected fasting urine samples, which were used for metabolomic profiling (Ultrahigh Performance Liquid chromatography-Mass Spectrometry). Multivariable logistic and ordinal logistic regression models were used for analysis, accounting for gender, age, body mass index and use of AREDS supplementation. Results from both cohorts were then meta-analyzed. No significant differences in urine metabolites were seen when comparing patients with AMD and controls. When disease severity was considered as an outcome, six urinary metabolites differed significantly (p < 0.01). In particular, two of the metabolites identified have been previously shown by our group to also differ in the plasma of patients of AMD compared to controls and across severity stages. While there are fewer urinary metabolites associated with AMD than plasma metabolites, this study identified some differences across stages of disease that support previous work performed with plasma, thus highlighting the potential of these metabolites as future biomarkers for AMD.

Efficacy and Safety of Intravitreal Aflibercept Treat and Extend for Polypoidal Choroidal Vasculopathy in the ATLANTIC Study: A Randomized Clinical Trial.

IMPORTANCE: Polypoidal choroidal vasculopathy (PCV) is far less common and studied in a Caucasian population than in an Asian population, and the optimal treatment approach remains to be confirmed. METHODS: A 52-week, double-masked, sham-controlled, phase 4, investigator-initiated randomized clinical trial (RCT) in naive symptomatic Caucasian patients with PCV treated with aflibercept in a treat-and-extend regimen (T&E) (intravitreal aflibercept injection [IVAI] T&E). Patients were randomized at week 16 to receive IVAI T&E plus either sham photodynamic therapy (PDT) or standard fluence PDT with verteporfin. The main outcome measures were changes in best-corrected visual acuity (BCVA) from baseline to 52 weeks and polyp occlusion at week 52. Data are presented as median (interquartile range [IQR]) for BCVA, number of IVAI, and change in central retinal thickness (CRT). RESULTS: Of the 50 patients included in the study, 48 patients completed the 52 weeks of follow-up. During this period, a significant median (IQR) BCVA gain of 6 [2-12] Early Treatment Diabetic Retinopathy Study letters was observed for all patients (p < 0.001), after 8 (7-9) injections, with a significant reduction of -93.0 [-154.0, -44.0] µm in central macular thickness (p < 0.001). Using indocyanine green angiography, a complete occlusion of polypoidal lesions was documented in 72% of the cases. Still, no significant difference was detected between the sham PDT and the aflibercept PDT arms, at week 52, for BCVA change (6.5 [2-11] vs. 5 [2-13] letters (p = 0.98)), number of IVAIs (8.5 [7-9] vs. 8 [7-9] (p = 0.21)), change in CRT (-143 [-184; -47] vs. -89 [-123; -41.5] µm [p = 0.23]), and rates of complete polyp occlusion: 77 versus 68% (p = 0.53) or presence of fluid: 68 versus 57% (p = 0.56). No serious ocular adverse events were registered in the 2 arms. CONCLUSIONS AND RELEVANCE: To our knowledge, this is the first RCT to compare aflibercept T&E monotherapy with aflibercept T&E plus verteporfin PDT in a Caucasian population with PCV. Aflibercept monotherapy in a T&E showed to be effective and safe with a significant median BCVA improvement of 6 letters and a complete occlusion of polypoidal lesions in near 3 quarters of the eyes, at 1 year. As only 22% of the eyes underwent PDT treatment, the benefit of combined treatment for PCV in Caucasian patients could not be definitively elucidated from this study. TRIAL REGISTRATION: The clinical trial was registered in ClinicalTrials.gov Identifier NCT02495181 and the European Union Drug Regulating Authorities Clinical Trials Database EudraCT No. 2015-001368-20.

Characterization of One-Year Progression of Risk Phenotypes of Diabetic Retinopathy.

INTRODUCTION: We characterized the progression of different diabetic retinopathy (DR) phenotypes in type 2 diabetes (T2D). METHODS: A prospective longitudinal cohort study (CORDIS, NCT03696810) was conducted with three visits (baseline, 6 months, and 1 year). Demographic and systemic data included age, sex, diabetes duration, lipid profile, and hemoglobin A1c (HbA1c). Ophthalmological examinations included best-corrected visual acuity (BCVA), color fundus photography (CFP), and optical coherence tomography (OCT and OCTA). Phenotype classification was performed at the 6-month visit based on microaneurysm turnover (MAT, on CFP) and central retinal thickness (CRT, on OCT). Only risk phenotypes B (MAT < 6 and increased CRT) and C (MAT ≥ 6 with or without increased CRT) were included. ETDRS grading was performed at the baseline visit based on seven-field CFP. RESULTS: A total of 133 T2D individuals were included in the study; 81 (60%) eyes were classified as phenotype B and 52 (40%) eyes as phenotype C. Of these, 128 completed the 1-year follow-up. At baseline, eyes with phenotype C showed greater capillary closure (superior capillary plexus, deep capillary plexus, and full retina, p < 0.001) and increased foveal avascular zone (FAZ) area (p < 0.001), indicating more advanced microvascular disease. Neurodegeneration represented by thinning of the ganglion cell layer + inner plexiform layer (GCL + IPL) was present in both phenotypes. When analyzing the 1-year progression of each phenotype, only phenotype C revealed a significant decrease in BCVA (p = 0.02) and enlargement of the FAZ (p = 0.03). A significant progressive decrease in the vessel density of the deep capillary layer and in MAT occurred in both phenotypes, but these changes were particularly relevant in phenotype C and ETDRS grades 43-47. During the 1-year period, both phenotypes B and C showed progression in GCL + IPL thinning (p < 0.001). CONCLUSIONS: In the 1-year period of follow-up, both phenotypes B and C showed progression in retinal neurodegeneration, whereas phenotype C showed more marked disease progression at the microvascular level.

T and genetic variations between Asian and Caucasian polypoidal choroidal vasculopathy.

PURPOSE: To compare phenotypic and genetic variations in polypoidal choroidal vasculopathy (PCV) between Caucasian and Asian patients. METHODS: We analysed phenotypic and genotypic data from two sites, Association for Innovation and Biomedical Research on Light and Image, Portugal and Singapore National Eye Centre, Singapore. Baseline fundus photography, spectral domain-optical coherence tomography, indocyanine green and fluorescein angiography scans were analysed by respective reading centres using a standardised grading protocol. Single nucleotide polymorphisms across 8 PCV loci were compared between cases and controls selected from each population. RESULTS: One hundred and forty treatment-naïve PCV participants (35 Portuguese and 105 Singaporean) were included. The Portuguese cohort were older (72.33±8.44 vs 68.71±9.40 years, p=0.043) and were comprised of a lower proportion of males (43% vs 71%, p=0.005) compared with the Singaporean cohort. Differences in imaging features include higher prevalence of soft drusen (66% vs 30%, p=0.004), lower prevalence of subretinal haemorrhage (14% vs 67%, p<0.001), smaller polypoidal lesion (PL) area (0.09±0.09 vs 0.76±0.93 mm2, p<0.001), lower ratio of PL to branching vascular network area (3% vs 38%, p<0.001) and lower central retinal thickness (346.48±93.74 vs 493.16±212.92 µm, p<0.001) in the Portuguese cohort. CETP rs3764261 (OR 2.467; 95% CI 1.282 to 4.745, p=0.006) in the Portuguese population was significantly associated with PCV and CFH rs800292 (OR 1.719; 95% CI 1.139 to 2.596, p=0.010) in the Singaporean population, respectively. CONCLUSION: Among Asian and Caucasian patients with PCV, there are significant differences in the expression of phenotype. We also identified different polymorphisms associated with PCV in the two populations.

Spherical harmonics representation of the potential energy surface for the H2⋯H2 van der Waals complex.

We perform a study of the molecular anisotropy for the H2⋯H2 van der Waals system using a spherical harmonics expansion. We use six leading stable configurations to construct our analytical potential energy surface (PES) from ab initio calculations guided qualitatively by the symmetry-adapted perturbation theory (SAPT) analyses. We extrapolate the energies of the PES performed at the CCSD(T)/aug-cc-pVnZ (n = 2 and 3) levels to the complete basis set (CBS) limit. To best fit the shallow potential energy surface of each leading configuration with the intermolecular distance, it was employed an extended version of the Rydberg potential. To assess the quality of our extrapolated analytical PES, we calculate the second virial coefficients, which are in relatively good agreement with the experimental data. As a result, the spherical harmonics coefficients obtained might be of considerable relevance in spectroscopy and dynamics applications.

Age-Related Macular Degeneration Staging by Color Fundus Photography vs. Multimodal Imaging-Epidemiological Implications (The Coimbra Eye Study-Report 6).

Epidemiology of age-related macular degeneration (AMD) is based on staging systems relying on color fundus photography (CFP). We aim to compare AMD staging using CFP to multimodal imaging with optical coherence tomography (OCT), infra-red (IR), and fundus autofluorescence (FAF), in a large cohort from the Epidemiologic AMD Coimbra Eye Study. All imaging exams from the participants of this population-based study were classified by a central reading center. CFP images were graded according to the International Classification and Grading System for AMD and staged with Rotterdam classification. Afterward, CFP images were reviewed with OCT, IR, and FAF and stage update was performed if necessary. Early and late AMD prevalence was compared in a total of 1616 included subjects. In CFP-based grading, the prevalence was 14.11% for early AMD (n = 228) and 1.05% (n = 17) for late AMD, nine cases (0.56%) had neovascular AMD (nAMD) and eight (0.50%) geographic atrophy (GA). Using multimodal grading, the prevalence increased to 14.60% for early AMD (n = 236) and 1.61% (n = 26) for late AMD, with 14 cases (0.87%) of nAMD and 12 (0.74%) of GA. AMD staging was more accurate with the multimodal approach and this was especially relevant for late AMD. We propose that multimodal imaging should be adopted in the future to better estimate and compare epidemiological data in different populations.

Prevalence of malnutrition among children and women of reproductive age in Uruguay by socio-economic status and educational level.

OBJECTIVE: To describe the magnitude and distribution of malnutrition in all forms (stunting, wasting, overweight and obesity) by level of education and socio-economic status (SES). DESIGN: Representative data from three national surveys were used: the socio-economic characteristics of Uruguayan households the 2012-2013; the Survey of Child Health, Nutrition and Development and the Survey of Chronic Disease Risks. We defined overweight, obesity, wasting/underweight and stunting/short stature according to WHO criteria. We conducted a comparison between malnutrition prevalence values per SES and education level. SETTING: In total, 1 183 177 households were surveyed, including 2265 children's and 752 women's households, forming a nationally representative sample in urban areas with more than 5000 habitants. PARTICIPANTS: A total of 3079 children aged <4 years from the National Survey of Child Health, Nutrition and Development 2013 and 752 women aged 20-49 years from the National Survey of Chronic Disease Risks 2013 were included. RESULTS: Among children aged <4 years, stunting and overweight disproportionately affected low-wealth groups, with 5·45 % of children in the lower income tertile and 3·44 % in the upper tertile presenting stunting (P < 0·05). Overweight and obesity were higher in the third tertile of income. Among the women, 54·8 % (95 % CI 48·0, 61·6) had excess weight (overweight and obesity) and significant differences were found between those with the lowest and highest levels of SES. Regarding excess weight with respect to educational level, significant differences were also found between the low and high levels and between the medium and high levels. CONCLUSIONS: In Uruguay, there are slight differences in the prevalence of all forms of malnutrition according to SES and education levels in the populations considered. Excess weight in children and women poses the greatest public health nutritional challenge at all levels of SES and education. The fact that more educated mothers are more overweight differs from the findings in other countries and should be studied in more detail. Stunting in children is also important, requiring more focused interventions. Notably, excess weight is higher in more educated mothers, a fact that differs from other countries. Further analysis is important to understand this discrepancy.

Higher Intake of Polyunsaturated Fatty Acid and Monounsaturated Fatty Acid is Inversely Associated With AMD.

Purpose: To evaluate the association between dietary fat intake and the presence of AMD. Methods: Cross-sectional, observational study with cohorts prospectively recruited from the United States and Portugal. AMD was diagnosed based on color fundus photographs with the AREDS classification. A validated food frequency questionnaire was used to calculate the percent energy intake of trans fat, saturated fat, monounsaturated fatty acid (MUFA), and polyunsaturated fatty acid (PUFA). Odds ratio (OR) and 95% confidence intervals for quintile of amount of FA were calculated. Multiple logistic regression was used to estimate the OR. Results: We included 483 participants, 386 patients with AMD and 97 controls. Higher intake of trans fat was associated with a 2.3-fold higher odds of presence of AMD (P for trend = 0.0156), whereas a higher intake of PUFA (OR, 0.25; P for trend = 0.006) and MUFA (OR, 0.24; P for trend < 0.0001) presented an inverse association. Subgroup analysis showed that higher quintile of trans fat was associated with increased odds of having intermediate AMD (OR, 2.26; P for trend = 0.02); and higher quintile of PUFA and MUFA were inversely associated with intermediate AMD (OR, 0.2 [P for trend = 0.0013]; OR, 0.17 [P for trend < 0.0001]) and advanced AMD (OR, 0.13 [P for trend = 0.02]; OR, 0.26 [P for trend = 0.004]). Additionally, a statistically significant effect modification by country was noted with inverse association between MUFA and AMD being significant (OR, 0.04; P for trend < 0.0001) for the Portugal population only. Conclusions: Our study shows that higher dietary intake of trans fat is associated with the presence of AMD, and a higher intake of PUFA and MUFA is inversely associated with AMD.

Is living near green areas beneficial to mental health? Results of the Pró-Saúde Study.

OBJECTIVE: To investigate the association between exposure to green areas in the surroundings of the residence and the presence of common mental disorders among adults, according to different income strata. METHODS: Cross-sectional study with 2,584 participants from the Pró-Saúde Study (2006), residing in the city of Rio de Janeiro. Common Mental Disorders were measured using the General Health Questionnaire (GHQ-12) and exposure to green areas was measured using the normalized difference vegetation index, in buffers with radiuses between 100 and 1,500 meters around the residence. We used the mean and maximum normalized difference vegetation index categorized into quartiles. The study population was divided into three subgroups, according to the income: low, intermediate, and high. Odds ratios and their 95% confidence intervals were estimated with logistic regression models. The models were adjusted by sex and age, with and without inclusion of physical activity practice. RESULTS: The proportion of common mental disorders was 30% and 39% among men and women, respectively. The results of the adjusted models showed an inverse association between the presence of green areas in the surroundings of the residence and the occurrence of common mental disorders, in the buffer of 200 meters in the intermediate-income group and in the buffers of 400 and 1,500 meters in the low-income group. The odds ratio ranged from 0.52 (buffer of 1,500 meters) to 0.68 (buffer of 200 meters). The association found was independent of physical activity practice. CONCLUSIONS: The evidence found suggests the existence of a beneficial effect of urban green areas on the mental health of lower-income individuals. These findings can help in understanding how the urban environment can affect the mental health of the population.

Human Plasma Metabolomics in Age-Related Macular Degeneration: Meta-Analysis of Two Cohorts.

The pathogenesis of age-related macular degeneration (AMD), a leading cause of blindness worldwide, remains only partially understood. This has led to the current lack of accessible and reliable biofluid biomarkers for diagnosis and prognosis, and absence of treatments for dry AMD. This study aimed to assess the plasma metabolomic profiles of AMD and its severity stages with the ultimate goal of contributing to addressing these needs. We recruited two cohorts: Boston, United States (n = 196) and Coimbra, Portugal (n = 295). Fasting blood samples were analyzed using ultra-high performance liquid chromatography mass spectrometry. For each cohort, we compared plasma metabolites of AMD patients versus controls (logistic regression), and across disease stages (permutation-based cumulative logistic regression considering both eyes). Meta-analyses were then used to combine results from the two cohorts. Our results revealed that 28 metabolites differed significantly between AMD patients versus controls (false discovery rate (FDR) q-value: 4.1 × 10-2-1.8 × 10-5), and 67 across disease stages (FDR q-value: 4.5 × 10-2-1.7 × 10-4). Pathway analysis showed significant enrichment of glycerophospholipid, purine, taurine and hypotaurine, and nitrogen metabolism (p-value ≤ 0.04). In conclusion, our findings support that AMD patients present distinct plasma metabolomic profiles, which vary with disease severity. This work contributes to the understanding of AMD pathophysiology, and can be the basis of future biomarkers and precision medicine for this blinding condition.