The Classification Systems in Psychiatry in a Phase of Crisis? Focus on DSM-5

a) Baseado num trabalho apresentado oralmente no 7º Simpósio do Serviço de Psiquiatria do Hospital Professor Doutor Fernando Fonseca EPE, que teve lugar a 10 e 11 de Março de 2017.A história das classificações psiquiátricas norte-americanas ilustra o percurso classificatório que se iniciou nos anos 60 a partir do caos em que estava imersa a questão do diagnóstico. Os dois primeiros sistemas (DSM-I e DSM-II) estavam influenciados pela escola psicoanalítica. Após a introdução do DSM-III em 1980 emergiu o paradigma neo-Kraepeliniano e o modelo médico de doença. Apesar de ter introduzido um maior rigor na definição e descrição das entidades nosológicas, revelou as suas limitações em termos da validade. As criticas a este paradigma levaram à argumentação de que o sistema classificativo mostrava sintomas de crise num sentido Kuhniano e, por este motivo poderia ter chegado o momento de uma revolução paradigmática. A revisão do DSM-IV e a implementação do DSM-5 em 2013 mostraram que este objectivo é, por enquanto, inalcançável. O resultado final é um sistema “híbrido” que já demonstrou a sua vulnerabilidade tal o nível de crítica e refutação em cursoinfo:eu-repo/semantics/publishedVersio

Sequential Morphological Changes in the CNV Net after Intravitreal Anti-VEGF Evaluated with OCT Angiography

PURPOSE: To assess and describe sequential morphological changes in the choroidal neovascularization (CNV) net using optical coherence tomography angiography (OCTA) in patients undergoing treatment with intravitreal antivascular endothelial growth factor (VEGF). METHODS: Prospective cohort study. OCTA was performed sequentially: before (t0), 1 h (t1), 1 week (t2) and 1 month after the injection (t3), using Avanti RTVue XR equipped with the AngioVue® software (Optovue, Calif., USA). All images were classified by two independent graders. RESULTS: Ten eyes of 10 patients, with a mean age of 72.4 ± 10.5 years, were included. CNV morphology was described as tree-like in 5 eyes, glomerular in 1 and fragmented in 4. A fibrovascular capsule surrounding the CNV net was found in 4 eyes and a feeder trunk was noticed in 6. No changes were observed at t1. Loss of peripheral capillaries, vessel fragmentation and decreased vessel density were evident in 8 eyes at t2. The CNV capillary density and the peripheral anastomosis increased in all of these at t3. Two eyes remained unchanged through the whole length of follow-up. CONCLUSIONS: Significant changes in the CNV net can be observable in OCTA at least 1 week after intravitreal anti-VEGF. The safety of frequent examinations may provide a method of gauging treatment effects

Long-term follow-up of myopic choroidal neovascularization treated with ranibizumab

PURPOSE: To evaluate the long-term safety and efficacy of intravitreal ranibizumab in the treatment of myopic choroidal neovascularization (CNV). METHODS: Three-year retrospective, nonrandomized, interventional case series. Forty eyes of 39 patients with myopic CNV were included; 15 with previous photodynamic therapy, and 25 naïve eyes. Best-corrected visual acuity (BCVA) changes, central foveal thickness (CFT), and number of treatments were assessed, from baseline to month 36. RESULTS: Mean visual acuity improved from 55.4 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at baseline to 59.7 letters at 12 months (p = 0.07), 61.8 letters at 24 months (p = 0.008) and 63.4 letters at 36 months (p = 0.039). Twenty-five percent of the patients gained ≥15 letters (3 lines) at 12 months, 30% at 24 months and 35% at 36 months. There was a mean reduction of 80 μm in CFT (p < 0.001). A mean of 4.1 injections were performed in the first year, 2.4 in the second year and 1.1 in the third year. Fifty-three percent of the eyes had no need for treatment during the third year of follow-up. CONCLUSIONS: Intravitreal ranibizumab seems to be an effective and safe therapeutic procedure to treat CNV in highly myopic eyes, with a high proportion of patients gaining or stabilizing BCVA at a 3-year follow-up.info:eu-repo/semantics/publishedVersio

Long-term chorioretinal changes after photodynamic therapy for chronic central serous chorioretinopathy

PURPOSE: To evaluate morphological and functional chorioretinal changes 5 years after standard photodynamic therapy (PDT) for chronic central serous chorioretinopathy (CSC). METHODS: A retrospective, nonrandomized study, including patients with chronic CSC treated with standard PDT and followed for at least 60 months. All patients underwent a complete ophthalmological examination, and the location and number of treatments were registered. Five or more years after treatment, subfoveal and non-subfoveal treated areas were evaluated with Spectralis optical coherence tomography and microperimetry. RESULTS: Seventeen eyes of 15 patients were included, with mean age of 48.3 ± 8.4 years and a mean follow-up of 80.6 ± 12.4 months (range from 62 to 104 months). All eyes had neurosensory detachment (NSD) at baseline. Treatment was performed under the fovea in 58.8 % and in a non-foveal area in 41.2 % of the eyes. At the final visit all eyes had resolution of the NSD, with a statistical significant reduction in central macular thickness (p = 0.005) and preserved neuroretinal thickness (p = 0.839). There was a statistical difference between initial and final BCVA (p < 0.001) and a mean gain of 8.4 ± 7.8 letters. Subfoveal morphological changes in external limiting membrane (ELM) and in photoreceptor inner and outer segment junction (IS/OS) were correlated with final BCVA (p = 0.015 and p = 0.014 respectively), but not with the variation of BCVA. There was a statistical correlation between morphological changes in IS/OS line and retinal sensitivity in the central 12° and 2° (p = 0.003 and p = 0.002 respectively). The morphological changes in the subfoveal layers were not dependent on treatment location (p = 0.154, p = 0.644, and p = 1.0 for ELM, IS/OS line, and retinal pigment epithelium respectively). Subfoveal final mean choroidal thickness was 295.1 ± 68.7 μm, and showed no statistical difference from the normal population (p = 0.633). CONCLUSIONS: Morphological and functional chorioretinal changes, observed 5 or more years after standard PDT for chronic CSC, were not correlated with the location of treatment, neither with the progression of visual acuity or with the location of treatment, and are more likely to be related to the disease itself than with the treatment provided.info:eu-repo/semantics/publishedVersio

Treatment of Retinal Vein Occlusion with Ranibizumab in Clinical Practice: Longer-Term Results and Predictive Factors of Functional Outcome

To evaluate long-term results and predictors of efficacy in patients with macular edema due to retinal vein occlusion (RVO) treated with intravitreal ranibizumab in a clinical practice setting.info:eu-repo/semantics/publishedVersio

Depression with melancholic features is associated with higher long-term risk for dementia

BACKGROUND: Depression has been reported to increase the risk of subsequently developing dementia, but the nature of this relation remains to be elucidated. Depression can be a prodrome/manifestation of dementia or an early risk factor, and the effect may differ according to depression subtypes. Our aim was to study the association between early-onset depression and different depression subtypes, and the later occurrence of dementia. METHODS: We conducted a cohort study including 322 subjects with depression, recruited between 1977 and 1984. A comparison cohort (non-exposed) was recruited retrospectively, to include 322 subjects admitted at the same hospital for routine surgery (appendicectomy or cholecystectomy), at the same period as the depressed cohort. Subjects were contacted again between 2009 and 2014, to assess their dementia status. We computed the risk for dementia in subjects with early onset depression and quantified the association between different depression subtypes (namely melancholic, anxious, and psychotic) and dementia. RESULTS: The odds of dementia were increased by 2.90 times (95% C.I. 1.61-5.21; p<0.0001) for the depressed cohort when compared to the surgical cohort. When the analysis was restricted to patients younger than 45 years old at baseline, the odds for dementia in the depressed cohort were also significantly higher when compared to the surgical cohort (8.53; 95% C.I. 2.40-30.16). In the multivariate Cox analysis, subjects having depression with melancholic features had an increased risk for developing dementia compared to those without melancholic features (HR=3.64; 95% C.I. 1.78-11.26; p=0.025). LIMITATIONS: About 59% of the participants with depression and 53% of those non-exposed were lost during follow up. The inclusion of biological biomarkers would strengthen the results. The sample included a low number of bipolar patients. CONCLUSIONS: These results support depression as an early risk factor for dementia. Depression with melancholic features was found as an important risk factor for dementia, playing a main role in the relation between these disorders

Dissecting the Relation between a Nuclear Receptor and GATA: Binding Affinity Studies of Thyroid Hormone Receptor and GATA2 on TSHβ Promoter

Background: Much is known about how genes regulated by nuclear receptors (NRs) are switched on in the presence of a ligand. However, the molecular mechanism for gene down-regulation by liganded NRs remains a conundrum. The interaction between two zinc-finger transcription factors, Nuclear Receptor and GATA, was described almost a decade ago as a strategy adopted by the cell to up-or down-regulate gene expression. More recently, cell-based assays have shown that the Zn-finger region of GATA2 (GATA2-Zf) has an important role in down-regulation of the thyrotropin gene (TSH beta) by liganded thyroid hormone receptor (TR). Methodology/Principal Findings: In an effort to better understand the mechanism that drives TSH beta down-regulation by a liganded TR and GATA2, we have carried out equilibrium binding assays using fluorescence anisotropy to study the interaction of recombinant TR and GATA2-Zf with regulatory elements present in the TSH beta promoter. Surprisingly, we observed that ligand (T3) weakens TR binding to a negative regulatory element (NRE) present in the TSH beta promoter. We also show that TR may interact with GATA2-Zf in the absence of ligand, but T3 is crucial for increasing the affinity of this complex for different GATA response elements (GATA-REs). Importantly, these results indicate that TR complex formation enhances DNA binding of the TR-GATA2 in a ligand-dependent manner. Conclusions: Our findings extend previous results obtained in vivo, further improving our understanding of how liganded nuclear receptors down-regulate gene transcription, with the cooperative binding of transcription factors to DNA forming the core of this process.Medical Research Council (MRC), UKConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Brazi

Models of Star-Planet Magnetic Interaction

Magnetic interactions between a planet and its environment are known to lead to phenomena such as aurorae and shocks in the solar system. The large number of close-in exoplanets that were discovered triggered a renewed interest in magnetic interactions in star-planet systems. Multiple other magnetic effects were then unveiled, such as planet inflation or heating, planet migration, planetary material escape, and even modification of the host star properties. We review here the recent efforts in modelling and understanding magnetic interactions between stars and planets in the context of compact systems. We first provide simple estimates of the effects of magnetic interactions and then detail analytical and numerical models for different representative scenarii. We finally lay out a series of future developments that are needed today to better understand and constrain these fascinating interactions.Comment: 23 pages, 10 figures, accepted as a chapter in the Handbook of Exoplanet

Structural Insights into Human Peroxisome Proliferator Activated Receptor Delta (PPAR-Delta) Selective Ligand Binding

Peroxisome proliferator activated receptors (PPARs δ, α and γ) are closely related transcription factors that exert distinct effects on fatty acid and glucose metabolism, cardiac disease, inflammatory response and other processes. Several groups developed PPAR subtype specific modulators to trigger desirable effects of particular PPARs without harmful side effects associated with activation of other subtypes. Presently, however, many compounds that bind to one of the PPARs cross-react with others and rational strategies to obtain highly selective PPAR modulators are far from clear. GW0742 is a synthetic ligand that binds PPARδ more than 300-fold more tightly than PPARα or PPARγ but the structural basis of PPARδ:GW0742 interactions and reasons for strong selectivity are not clear. Here we report the crystal structure of the PPARδ:GW0742 complex. Comparisons of the PPARδ:GW0742 complex with published structures of PPARs in complex with α and γ selective agonists and pan agonists suggests that two residues (Val312 and Ile328) in the buried hormone binding pocket play special roles in PPARδ selective binding and experimental and computational analysis of effects of mutations in these residues confirms this and suggests that bulky substituents that line the PPARα and γ ligand binding pockets as structural barriers for GW0742 binding. This analysis suggests general strategies for selective PPARδ ligand design