The phenotypic spectrum associated with OTX2 mutations in humans

OBJECTIVE: The transcription factor OTX2 is implicated in ocular, craniofacial, and pituitary development. DESIGN: We aimed to establish the contribution of OTX2 mutations in congenital hypopituitarism patients with/without eye abnormalities, study functional consequences, and establish OTX2 in the human brain, with a view to investigating the mechanism of action. METHODS: We screened patients from the UK (n=103), international centers (n=24), and Brazil (n=282); 145 were within the septo-optic dysplasia spectrum, and 264 had no eye phenotype. Transactivation ability of OTX2 variants was analysed in murine hypothalamic GT1-7 neurons. In situ hybridization was performed on human embryonic brain sections. Genetically engineered mice were generated with a series of C-terminal OTX2 variants. RESULTS: Two chromosomal deletions and six haploinsufficient mutations were identified in individuals with eye abnormalities; an affected relative of one patient harboured the same mutation without an ocular phenotype. OTX2 truncations led to significant transactivation reduction. A missense variant was identified in another patient without eye abnormalities, however studies revealed it was most likely not causative. In the mouse, truncations proximal to aa219 caused anophthalmia, while distal truncations and the missense variant were tolerated. During human embryogenesis, OTX2 was expressed in the posterior pituitary, retina, ear, thalamus, choroid plexus, and partially in the hypothalamus, but not in the anterior pituitary. CONCLUSIONS: OTX2 mutations are rarely associated with hypopituitarism in isolation without eye abnormalities, and may be variably penetrant, even within the same pedigree. Our data suggest that the endocrine phenotypes in patients with OTX2 mutations are of hypothalamic origin

Mapping geographical inequalities in access to drinking water and sanitation facilities in low-income and middle-income countries, 2000-17

Background Universal access to safe drinking water and sanitation facilities is an essential human right, recognised in the Sustainable Development Goals as crucial for preventing disease and improving human wellbeing. Comprehensive, high-resolution estimates are important to inform progress towards achieving this goal. We aimed to produce high-resolution geospatial estimates of access to drinking water and sanitation facilities. Methods We used a Bayesian geostatistical model and data from 600 sources across more than 88 low-income and middle-income countries (LMICs) to estimate access to drinking water and sanitation facilities on continuous continent-wide surfaces from 2000 to 2017, and aggregated results to policy-relevant administrative units. We estimated mutually exclusive and collectively exhaustive subcategories of facilities for drinking water (piped water on or off premises, other improved facilities, unimproved, and surface water) and sanitation facilities (septic or sewer sanitation, other improved, unimproved, and open defecation) with use of ordinal regression. We also estimated the number of diarrhoeal deaths in children younger than 5 years attributed to unsafe facilities and estimated deaths that were averted by increased access to safe facilities in 2017, and analysed geographical inequality in access within LMICs. Findings Across LMICs, access to both piped water and improved water overall increased between 2000 and 2017, with progress varying spatially. For piped water, the safest water facility type, access increased from 40.0% (95% uncertainty interval [UI] 39.4-40.7) to 50.3% (50.0-50.5), but was lowest in sub-Saharan Africa, where access to piped water was mostly concentrated in urban centres. Access to both sewer or septic sanitation and improved sanitation overall also increased across all LMICs during the study period. For sewer or septic sanitation, access was 46.3% (95% UI 46.1-46.5) in 2017, compared with 28.7% (28.5-29.0) in 2000. Although some units improved access to the safest drinking water or sanitation facilities since 2000, a large absolute number of people continued to not have access in several units with high access to such facilities (>80%) in 2017. More than 253 000 people did not have access to sewer or septic sanitation facilities in the city of Harare, Zimbabwe, despite 88.6% (95% UI 87.2-89.7) access overall. Many units were able to transition from the least safe facilities in 2000 to safe facilities by 2017; for units in which populations primarily practised open defecation in 2000, 686 (95% UI 664-711) of the 1830 (1797-1863) units transitioned to the use of improved sanitation. Geographical disparities in access to improved water across units decreased in 76.1% (95% UI 71.6-80.7) of countries from 2000 to 2017, and in 53.9% (50.6-59.6) of countries for access to improved sanitation, but remained evident subnationally in most countries in 2017. Interpretation Our estimates, combined with geospatial trends in diarrhoeal burden, identify where efforts to increase access to safe drinking water and sanitation facilities are most needed. By highlighting areas with successful approaches or in need of targeted interventions, our estimates can enable precision public health to effectively progress towards universal access to safe water and sanitation. Copyright (C) 2020 The Author(s). Published by Elsevier Ltd.Peer reviewe

The performance of various anthropometric assessment methods for predicting low birth weight in pregnant women Desempenho de diferentes métodos de avaliação antropométrica de gestantes na predição de baixo peso ao nascer

OBJECTIVES: to assess the performance of various anthropometric methods for the evaulation of the nutritional status of pregnant women as a means of predicting low birth weight (LBW). METHODS: a descriptive cross-cutting study carried out among 433 pregnant women (>20 years) attending a Public Maternity Hospital in Rio de Janeiro, Brazil. The adequacy of the weight gain at the end of the pregnancy was evaluated in accordance with the proposals of the Institute of Medicine and the Brazilian Ministry of Health. The sensitivity, specificity and accuracy of the adequacy of weight gain at the end of the pregnancy or nutritional state of mother as a predictor of low birth weight were calculated. RESULTS: the sensitivity of the various methods varied from 63.1% to 68.4% and the specificity from 71.2% to 75.1%. The adapted Institute of Medicine proposal drawn up by the Brazilian Ministry of Health, according to the classification of the pre-delivery nutritional status of the mother according to the World Health Organization cutoff points showed itself to be the most accurate (74.5%), this being the most adequate method for nutritional triage for reason of its association with low birth weight (OR=4.10; 95%CI=1.53-10.92). CONCLUSIONS: the best proposals for this population are those of the Institute of Medicine and the Brazilian Ministry of Health. Further studies aiming to ascertain the most appropriate methods of anthropometric evaluation for different populations should be encouraged.<br>OBJETIVOS: avaliar o desempenho de diferentes métodos antropométricos para avaliação nutricional de gestantes para predizer o baixo peso ao nascer (BPN). MÉTODOS: estudo descritivo do tipo transversal, realizado com 433 puérperas (>20 anos) atendidas numa Maternidade Pública do Rio de Janeiro, Brasil. A adequação do ganho de peso ao final da gestação foi avaliada segundo as propostas do Institute of Medicine e do Ministério da Saúde. Calculou-se a sensibilidade, a especificidade e a acurácia das variáveis adequação do ganho de peso gestacional total ou adequação do estado nutricional materno ao final da gestação na predição do BPN. RESULTADOS: a sensibilidade dos métodos variou de 63,1% a 68,4% e a especificidade de 71,2% a 75,1%. A adaptação da proposta do Institute of Medicine elaborada pelo Ministério da Saúde, segundo a classificação do estado nutricional pré-gestacional pelos pontos de corte da Organização Mundial da Saúde apresentou maior acurácia (74,5%), sendo este último o mais adequado para triagem nutricional pela sua associação com o BPN (OR=4,10; IC95%=1,53-10,92). CONCLUSÕES: os melhores para esta população foram as propostas do Institute of Medicine e do Ministério da Saúde. Estudos visando reconhecer os métodos de avaliação antropométrica mais adequados na gestação devem ser estimulados em diferentes populações

Apoio social e saúde: pontos de vista das ciências sociais e humanas Social support and health: standpoints from the social and human sciences

Analisam-se os temas e as abordagens teórico-conceituais do apoio social nos artigos de importantes periódicos internacionais de ciências sociais e de medicina e nacionais de Saúde Coletiva/Saúde Pública no período 1983-2005. Procedeu-se a leitura dos resumos dos 259 textos internacionais e 57 nacionais encontrados classificando e computando as relações do apoio social com a saúde/doença/cuidado. A seguir analisaram-se os conceitos e as abordagens do apoio social do ponto de vista das teorias e dos autores das ciências sociais e humanas, em uma amostra intencional de 56 textos internacionais e 18 nacionais. A literatura internacional respalda-se na psicologia social, nas várias correntes da sociologia e da ciência política e menos na antropologia. A literatura nacional dialoga menos com as teorias psicossociais e mais com as sociológicas e as antropológicas, realçando-se pela abordagem do apoio com a rede social, a solidariedade, as trocas e os valores culturais, deslocando-se da esfera individual e privada para a capacidade de organização da sociedade civil e de ações coletivas. Diferentes correntes norteiam as análises teórico-conceituais do apoio social, sendo a literatura internacional mais antiga, diversificada, empírica e escassa de produção antropológica.<br>This article analyses the themes and conceptual-theoretical approaches of the social support in the literature from important international journals about social sciences and medicine, and in from 1983 to 2005 are analyzed. 259 international and 57 national abstracts was reading for the identification and computing the relations of the social support with health/disease/care. A deeper conceptual analysis about social support and the theories of social science were reported in an intentional sample of 56 international and 18 national texts. The international literature is based on the social psychology, in the several trends of the sociology and of the political science and less in the anthropology. The national literature dialogues less with the psychosocial theories and more with the sociological and anthropological theories. In this latter literature the social support approaches are concerned with social network theories; reciprocity, exchanges and cultural values. It is concluded that different trends guide the conceptual-theoretical analyses of the social support, being the international literature older, wider, more diversified and empirical, but with scarce anthropological production. The national literature is more reflexive them empirical

Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017

202401 bckwVersion of RecordOthersBill & Melinda Gates FoundationPublishedC