Diet-induced Maternal Obesity Alters Insulin Signalling In Male Mice Offspring Rechallenged With A High-fat Diet In Adulthood

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Modern lifestyle has resulted in an increase in the prevalence of obesity and its comorbidities in pregnant women and the young population. It has been well established that the consumption of a high-fat diet (HFD) has many direct effects on glucose metabolism. However, it is important to assess whether maternal consumption of a HFD during critical periods of development can lead to metabolic changes in the offspring metabolism. This study evaluated the potential effects of metabolic programming on the impairment of insulin signalling in recently weaned offspring from obese dams. Additionally, we investigated if early exposure to an obesogenic environment could exacerbate the impairment of glucose metabolism in adult life in response to a HFD. Swiss female mice were fed with Standard Chow (SC) or a HFD during gestation and lactation and tissues from male offspring were analysed at d28 and d82. Offspring from obese dams had greater weight gain and higher adiposity and food intake than offspring from control dams. Furthermore, they showed impairment in insulin signalling in central and peripheral tissues, which was associated with the activation of inflammatory pathways. Adipose tissue was ultimately the most affected in adult offspring after HFD rechallenge; this may have contributed to the metabolic deregulation observed. Overall, our results suggest that diet-induced maternal obesity leads to increased susceptibility to obesity and impairment of insulin signalling in offspring in early and late life that cannot be reversed by SC consumption, but can be aggravated by HFD re-exposure.118Sao Paulo Research Foundation (FAPESP) [2011/22156-7, 2013/12003-4]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Lipid Overload During Gestation And Lactation Can Independently Alter Lipid Homeostasis In Offspring And Promote Metabolic Impairment After New Challenge To High-fat Diet

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Nutritional status in early life is critically involved in the metabolic phenotype of offspring. However the changes triggered by maternal consumption of high-fat diet (HFD) in pre- or postnatal period should be better understood. Here we evaluated whether maternal HFD consumption during gestation and lactation could differently affect liver miR-122 and miR-370 expression leading to metabolic damages observed in offspring. Moreover, we investigate whether early overnutrition program offspring to more harmful response to HFD in later life. Methods: Female mice were fed either a standard chow (SC) diet or a HFD three weeks before and during mating, gestation and/or lactation. Offspring were evaluated on the delivery day (d0), in a cross-fostering model at day 28 (d28) and in adult life, after a re-challenge with a HFD (d82). Results: In vitro analysis using liver cell line showed that palmitate could induced decrease in miR-122 and increase in miR-370 expression. Newborn pups (d0) from obese dams showed a decrease in lipid oxidation markers (Cpt1a and Acadvl), an increase in triacylglycerol synthesis markers (Agpat and Gpam), as well as lower miR-122 and higher miR-370 hepatic content that was inversely correlated to maternal serum NEFA and TAG. Pups fostered to SC dams presented an increase in body weight and Agpat/Gpam expression at d28 compared to pups fostered to HFD dams and an inverse correlation was observed between miR-122 hepatic expression and offspring serum TAG. In adult life (d82), the reintroduction of HFD resulted in higher body weight gain and hepatic lipid content. These effects were accompanied by impairment in lipid and glucose metabolism, demonstrated by reduced Cpt1a/Acadvl and increased Agpat/Gpam expression, lower glucose tolerance and insulin sensitivity. Conclusion: Our data suggest that both gestational and lactation overnutrition results in metabolic changes that can permanently alter lipid homeostasis in offspring. The presence of fatty acids in maternal blood and milk seem to be responsible for modulating the expression of miR-122 and miR-370, which are involved in liver metabolism. These alterations significantly increase susceptibility to obesity and ectopic lipid accumulation and lead to a more harmful response to HFD in offspring.14Sao Paulo Research Foundation (FAPESP) [2011/22156-7, 2013/07607-8, 2014/18165-9]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

SATISFAÇÃO DOS USUÁRIOS DO RESTAURANTE UNIVERSITÁRIO DA UNIVERSIDADE FEDERAL DE SANTA MARIA: UMA ANÁLISE DESCRITIVA

Essa pesquisa tem por objetivo avaliar o nível de satisfação dos usuários do Restaurante Universitário da Universidade Federal de Santa Maria - RS, por meio de métodos estatísticos descritivos. Foi elaborado um questionário com questões de perfil, avaliação da satisfação e da importância em relação à 41 itens relacionados ao Restaurante Universitário. Os itens de satisfação apresentaram uma consistência interna de 0,93. Participaram da pesquisa, 1.855 usuários, entre alunos, docentes e técnicos administrativos. Observou-se que a maioria dos usuários é do sexo feminino, solteiros, situados na faixa etária de 17 a 30 anos, alunos sem o benefício socioeconômico, que cursam a graduação e almoçam em grupo. A maioria dos respondentes frequenta o restaurante entre o meio dia e uma hora da tarde, e até pelo menos três vezes por semana, onde o preço atrativo é a principal motivação para frequentá-lo. A maioria dos atributos foram avaliados de forma positiva, com destaque para a iluminação interna, o preço cobrado, a localização, a acessibilidade, as formas de pagamento, o atendimento, o tamanho do restaurante, a organização do buffet, o conforto e o layout. Com relação aos itens avaliados insatisfatoriamente, merecem destaque a ventilação, o abrigo contra o sol e a chuva e os itens relacionados com a demanda de usuários

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

Oral care and oropharyngeal and tracheal colonization by Gram-negative pathogens in children

Background: Critical care nursing interventions to oral care can reduce microorganisms in the oropharynx available for translocation.Objectives: To analyse the effect of 0.12% chlorhexidine digluconate on the colonization of oropharyngeal and tracheal secretions by Gram-negative pathogens in mechanically ventilated children.Methods: A randomized, controlled and double-blinded study was performed in the paediatric intensive care unit (PICU) of a Brazilian university hospital. Exclusion criteria included child age under 28 days, pneumonia diagnosis at admission, use of tracheostomy, PICU length of stay (LOS) less than 48 h and refusal to participate. Children were randomly allocated to the interventional group (IG), in which oral care with chlorhexidine was administered, or to the placebo group (PG), which received oral care without antiseptic use. the data were analysed through Pearson's chi(2) test, Fisher's exact and ANOVA tests with significance levels set at 0.05.Results: the demographic characteristics of the 74 children were not statistically different between groups. No between-group differences in oropharyx colonization by Gram-negative pathogens were identified (p = 0.316). Pathogens were isolated in the tracheal secretions of two (10.0%) children in the PG and four (19.0%) children in the IG (p = 0.355).Conclusion: the use of chlorhexidine did not significantly influence the colonization of oropharyngeal and tracheal secretions by Gram-negative pathogens of the studied sample.Relevance to clinical practice: This study demonstrated no influence of a specific antiseptic agent on colonization profile of mechanically ventilated children in PICU. Further research in this field is necessary to promote evidence-based nursing practice on oral care of critically ill children.Universidade Federal de São Paulo, Sch Nursing, Pediat Nursing Dept, Escola Paulista Enfermagem, BR-04024002 São Paulo, BrazilHosp São Paulo, Pediat Intens Care Unit, São Paulo, BrazilUniversidade Federal de São Paulo, Sch Nursing, Pediat Nursing Dept, Escola Paulista Enfermagem, BR-04024002 São Paulo, BrazilHosp São Paulo, Pediat Intens Care Unit, São Paulo, BrazilWeb of Scienc

Surveillance for azoles resistance in Aspergillus spp. highlights a high number of amphotericin B-resistant isolates

Aspergillus spp. are the most common invasive mould infection and are responsible for high mortality. Aspergillus fumigatus is currently of interest because resistance to azole antifungals has emerged. The Campinas University Hospital (HC-UNICAMP) receives high-risk patients susceptible to opportunistic infections but there have been no reports of resistant A.fumigatus. This study aimed to assess the susceptibility profile of Aspergillus isolates, specifically looking for azole resistance. ITS and -tubulin DNA sequencing was performed on 228 sequential clinical isolates. Broth microdilution susceptibility testing was performed for all isolates. A.fumigatus represented 74% of the isolates followed by Aspergillus flavus (12%). Nine A.fumigatus isolates from 9 different patients showed high MIC values to at least 1 azole, but cyp51A polymorphisms were detected in only 6 isolates and none correlated with known resistance mutations. The most troubling observation was that the minimum inhibitory concentration for amphotericin B was elevated (2mgL(-1)) in 87% of patients with A.flavus isolates and 43% with Aspergillusfumigatus isolates. Given that amphotericin B is used to treat azole-resistant infections, these data highlight the need for continuous surveillance in Aspergillus for all antifungal resistance to implement correct treatment strategies for the management of these pathogens616360365CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ157884/2014-7; 246701/2013-

Autophagy Proteins Are Modulated In The Liver And Hypothalamus Of The Offspring Of Mice With Diet-induced Obesity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Nutritional excess during pregnancy and lactation has a negative impact on offspring phenotype. In adulthood, obesity and lipid overload represent factors that compromise autophagy, a process of lysosomal degradation. Despite knowledge of the impact of obesity on autophagy, changes in offspring of obese dams have yet to be investigated. In this study, we tested the hypothesis that maternal obesity induced by a high fat diet (HFD) modulates autophagy proteins in the hypothalamus and liver of the offspring of mice. At birth (d0), offspring of obese dams (HFD-O) showed an increase in p62 protein and a decrease in LC3-II, but only in the liver. After weaning (d18), the offspring of HFD-O animals showed impairment of autophagy markers in both tissues compared to control offspring (SC-O). Between day 18 and day 42, both groups received a control diet and we observed that the protein content of p62 remained increased in the livers of the HFD-O offspring. However, after 82 days, we did not find any modulation in offspring autophagy proteins. On the other hand, when the offspring of obese dams that received an HFD from day 42 until day 82 (OH-H) were compared with the offspring from the controls that only received an HFD in adulthood (OC-H), we saw impairment in autophagy proteins in both tissues. In conclusion, this study describes that HFD-O offspring showed early impairment of autophagy proteins. Although the molecular mechanisms have not been explored, it is possible that changes in autophagy markers could be associated with metabolic disturbances of offspring. (C) 2016 Elsevier Inc. All rights reserved.343041Sao Paulo Research Foundation (FAPESP) [2011/51.205-6]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Neurological Phenotypes of Gene Variants: A Report of Four Novel Variants

IRF2BPL gene variants have recently been associated to developmental disability and epilepsy in children and movement disorders in adults. So far, only few cases have been reported; here we present four novel cases identified by exome sequencing, while investigating developmental delay, adult-onset cerebellar ataxia or regression

MEMÓRIAS DO PROCESSO DE IMPLANTAÇÃO DO CURSO DE NUTRIÇÃO DO CAMPUS UFRJ-MACAÉ PROFESSOR ALOISIO TEIXEIRA

O Curso de graduação em Nutrição do Campus UFRJ-Macaé foi implantado em agosto de 2009, visando formar profissionais generalistas, atendendo a Resolução CNE/CES nº 5, de 07 de novembro de 2001 que institui as Diretrizes Curriculares Nacionais para os Cursos de Graduação em Nutrição. O processo de criação e aprovação ocorreu por iniciativa da Congregação do Instituto de Nutrição Josué de Castro (INJC), em atendimento ao Programa de Apoio aos Planos de Reestruturação e Expansão das Universidades Federais (Reuni-Decreto nº 6.096, de 24 de abril de 2007). Neste contexto, o INJC designou as docentes, Elizabeth Accioly, Eliza Maria de Aquino Lacerda, Beatriz Gonçalves Ribeiro, Lucia Maria Jaeger de Carvalho, Maria Cristina de Jesus Freitas e Rita de Cássia Perreli, para se juntarem aos representantes da Faculdade de Medicina e da Escola de Enfermagem Anna Nery da UFRJ e discutirem a implantação do curso no processo de expansão da Universidade em Macaé. A partir desta Comissão de Acompanhamento da Implantação do Curso em Macaé, seguiu-se a aprovação da criação pelo Conselho de Ensino de Graduação (CEG, 21.05.2009); aprovação do Projeto Pedagógico do Curso pela Câmara de Currículos do CEG (15.07.2009). O Conselho Universitário (CONSUNI, 06.08.2009) aprovou o processo de criação e autorizou a implantação do curso. O modelo curricular do Curso de Nutrição, juntamente com os de Medicina e Enfermagem e Obstetrícia, seguiu uma linha inovadora e audaciosa para a UFRJ, propondo uma integração do Ciclo Básico destes cursos, com a inclusão das disciplinas “Biologias para a Saúde”, “Saúde da Comunidade I” e “Mecanismos Básicos de Saúde e Doença”, cujas turmas seriam compostas por discentes e docentes e com apoio técnico dos três cursos. O Curso de Nutrição abriu sua primeira turma no segundo semestre de 2009, recebendo dezoito alunos, das 20 vagas autorizadas; contando com seis docentes, tendo a Professora Drª Beatriz Gonçalves Ribeiro como a primeira coordenadora. Ainda em 2009, com apoio da Prefeitura de Macaé e com recursos da Reuni-UFRJ, o curso teve avanços expressivos na estruturação de laboratórios básicos e específicos para o ciclo profissional.  Apesar dos avanços, em 2010, o curso seguia ainda com déficit estruturais, incluindo a relevante ausência de um Restaurante Universitário e alojamento discente, o que corroborava para evasão, considerando o custo de vida na região, movida pela cadeia petrolífera. Entretanto, o corpo social do curso, trabalhou ao longo dos quatros anos com vistas ao seu processo de reconhecimento pelo MEC, o qual ocorreu em outubro de 2013 sob a coordenação da Professora Drª Kelse Tibau de Albuquerque, recebendo qualificação de excelência (nota 4,0) e demonstrando a força do seu corpo social para a implantação e consolidação do curso em Macaé. Em 2014, sob a coordenação da Professora Drª Angelica Nakamura, ocorreu a formatura da primeira turma do Curso. Hoje, sob coordenação da Professora Drª Laís Buriti de Barros, o curso conta com 47 egressos e continua buscando oferecer um curso de ensino superior de excelência, atendendo os pilares: Ensino, Pesquisa e Extensão.   Palavras-chave: nutrição, graduação, expansão universitária, Projeto Reuni

Folic Acid and Vitamin B12 Prevent Deleterious Effects of Rotenone on Object Novelty Recognition Memory and <i>Kynu</i> Expression in an Animal Model of Parkinson’s Disease

Parkinson’s disease (PD) is characterized by a range of motor signs, but cognitive dysfunction is also observed. Supplementation with folic acid and vitamin B12 is expected to prevent cognitive impairment. To test this in PD, we promoted a lesion within the substantia nigra pars compacta of rats using the neurotoxin rotenone. In the sequence, the animals were supplemented with folic acid and vitamin B12 for 14 consecutive days and subjected to the object recognition test. We observed an impairment in object recognition memory after rotenone administration, which was prevented by supplementation (p Kynu), whose product metabolizes neurotoxic metabolites often accumulated in PD as kynurenine. Supplementation prevented the decrease in Kynu expression induced by rotenone in the substantia nigra (p Kynu promoter. Instead, we suggest that folic acid and vitamin B12 increased global DNA methylation, reduced the expression of Kynu inhibitors, maintained Kynu-dependent pathway homeostasis, and prevented the memory impairment induced by rotenone. Our study raises the possibility of adjuvant therapy for PD with folic acid and vitamin B12