DNA methyltransferase expression (DNMT1, DNMT3a and DNMT3b) as a potential biomarker for anti-VEGF diabetic macular edema response

Funding Information: This project was partially supported by an IDI&CA grant IPL/2021/DiffMeDiME_ESTeSL by H&TRC- Health & Technology Research Center, ESTeSL- Escola Superior de Tecnologia da Saúde, Instituto Politécnico de Lisboa and by Retina Institute of Lisbon (IRL).Purpose: DNA methylation is involved in Diabetic Retinopathy progression showing a metabolic memory mechanism. However, the association of DNA methyltransferase with diabetic macular edema is still unknown. We aimed to describe the differences in DNA methyltransferase gene expression in patients with different diabetic macular edema responses. Methods: A total of 27 diabetic patients, aged 59–90 years, were prospectively enrolled in this cross-sectional study. The participants were classified into control group (CG, n = 11), diabetic macular edema responders (rDME, n = 9) and non-responder diabetic macular edema (nrDME, n = 7) after anti-vascular endothelial growth factor (anti-VEGF) treatment. Only cases with a complete ophthalmological examination, digital 133° color fundus, and SD-OCT assessments were used. After RNA extraction and first-strand cDNA synthesis, quantitative real-time PCR was performed with specific primers on the CFX Connect™ Real-Time PCR Detection System to assess differential transcriptional expression patterns. Results: The DNMT1 gene showed a positive correlation (r = 0.617; p = 0.043) with Best Corrected Visual Acuity (BCVA) in CG, a positive correlation (r = 0.917; p = 0.010) with HbA1c in nrDME and a negative correlation (r = −0.659; p = 0.049) with GCL-IPL thickness in rDME. DNMT3A gene showed a positive correlation (r = −0.890; p = 0.001) with Sub-foveal Choroidal thickness in rDME whereas DNMT3b gene showed a negative correlation (r = −0.815; p = 0.007) with HbA1c and RNFL (r = −0.664; p = 0.026) in CG. Conclusions: Patients with similar metabolic profile risk factors showed associated DNA methyltransferase transcriptional expression patterns differences fitting with the anti-VEGF diabetic macular edema response. Further studies are needed to clarify if these results (1) reflect disease evolution, (2) translate the therapeutic impact, (3) or can help to predict the therapeutic resistance profile.publishersversionepub_ahead_of_prin

Role of DNA methylation in persistent diabetic macular edema

Projeto ID&CA 2021_IPL/2021/DiffMeDiME_ESTeSLBackground: a) Disease duration and metabolic control are insufficient to understand Diabetic Macular Edema (DME), the leading cause of vision loss in people with diabetes; b) 30-40% of cases of DME do not respond optimally to AVEGF (loading phase); c) poor genetic association in DR development (<25% RD) and PDR progression (25-50%). Purpose: To study the role of DNA methyltransferase expression (DNMT1,DNMT3a, DNMT3b) in persistent diabetic macular edema.info:eu-repo/semantics/publishedVersio

DNA methylation in diabetic macular edema: first report

Projeto IPL/2021/DiffMeDiME_ESTeSLEnvelhecimento humano e estilos de vida tem contribuído para aumento da DM. Edema macular diabético (EMD), uma das manifestações oculares da RD, é a principal causa de perda de visão em pessoas diabéticas. 30-40% casos EMD não respondem da melhor forma aos AVEGF (loading phase). Resistência pode persistir após 12 meses tratamento (+/50%). Objetivo do estudo: Desenvolver uma caracterização multimodal não invasiva (SD OCT e OCT A) combinada com a avaliação da metilação de DNA de forma a pode esclarecer alguns mecanismos importantes da doença mas também para novas abordagens terapêuticas que contribuem para a medicina de precisão.info:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

An outbreak of malignant catarrhal fever in Sambar deer (Rusa unicolor)

ABSTRACT: Malignant catarrhal fever (MCF) is an infectious, pansystemic and highly fatal disease with wide geographic distribution. The species that are clinically prone to it include cattle, deer and bison. In Brazil, the disease in ruminants and deer is associated with the contact with sheep, especially during labor, when the fetal remains that are eliminated contain the ovine herpesvirus 2 (OvHV-2). The outbreak took place in a conservationist property in the city of Casimiro de Abreu/RJ, which hosted 23 Sambar deer, and, of these, 19 died, showing neurological signs. The deer lived in a location together with 15 male and female meat sheep. A female specimen of the Sambar deer (Rusa unicolor), aged approximately three years, which had presented with neurological clinical signs was referred to necropsy in the Setor de Anatomia Patológica at Universidade Federal Rural do Rio de Janeiro (SAP/UFRRJ). During necropsy, cerebrospinal fluid was sampled for analysis; fragments of several organs were fixated in 10% buffered formalin and processed for histopathological analysis. Fragments of occipital lobe, cerebellum and bulb were collected to perform the polymerase chain reaction (PCR). The diagnosis of this outbreak was based on epidemiological, clinical and pathological findings, and on the amplification of the OvHV-2 DNA through PCR. The histological changes were the base to confirm the MCF case and were characterized by degeneration of vascular endothelial cells, fibrinoid vasculitis, hyperplasia and necrosis of lymphoid organs. However, PCR was an important tool to confirm the diagnosis. MCF as an important disease with nervous symptomatology in deer

Epidemiological characteristics of Brazilian spotted fever in Minas Gerais State, Brazil, 2000-2008

Brazilian spotted fever is the most common rickettsiosis in Brazil, most prevalent in the States of São Paulo and Minas Gerais. The aim of this study was to describe the epidemiological characteristics of Brazilian spotted fever in Minas Gerais from 2000 to 2008. Of the 132 cases of Brazilian spotted fever, 53 patients died, representing a case-fatality rate of 40.2%. Males predominated, with 78.8% of confirmed cases, and median age was 26.5 years. Absence of rash was associated with increased risk of death (p = 0.005). Greater Metropolitan Belo Horizonte, Rio Doce Valley, and Zona da Mata accounted for 70.6% of the cases, which occurred mainly from May to November. There was an increase in the number of cases, which could suggest an expansion of the disease, but probably resulted from an increase in the health system's diagnostic capacity and sensitivity. Despite this improvement, the case-fatality rate remains high and with no apparent tendency to decrease, thus indicating the need for improved prevention and patient care