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

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

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

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

Efeitos da associação entre insulinoterapia e suplementação oral com L-glutamina sobre a morfofisiologia hepática de ratos Wistar diabéticos tipo 1

Orientador: Prof.ª Dr.ª Maria Raquel Marçal NataliTese (doutorado em Ciências Biológicas) - Universidade Estadual de Maringá, 2019Resumo: O diabetes mellitus tipo 1 (T1DM) é uma doença crônica resultante da destruição imunológica das células ?-pancreáticas, que leva a perda da secreção endógena de insulina. A incapacidade dos tecidos insulino-dependentes de captar glicose leva a desregulação do metabolismo hepático de glicose, o que resulta em hiperglicemia. Vários tipos de insulina são utilizados na reposição hormonal obrigatória de pacientes T1DM, que variam entre ultra-rápida, rápida, intermediaria e de longa duração. Por outro lado, o aminoácido L-glutamina (GLN) tem a capacidade de promover redução do estresse oxidativo e das complicações crônicas associadas ao T1DM, porém sua concentração plasmática encontra-se geralmente diminuída nestes pacientes. Isto abre a possibilidade de suplementação da GLN concomitante com a reposição hormonal com insulina. Avaliar os efeitos da reposição hormonal com Insulina Degludeca (longa duração - basal) ou Insulina Regular (duração rápida), associadas ou não à suplementação oral com GLN, sobre parâmetros fisiológicos e plasmáticos, estresse oxidativo, metabolismo hepático e sobre as características histológicas do fígado de ratos Wistar T1DM. Ratos Wistar machos (50 dias de idade) foram distribuídos em um grupo padronização (P) e sete grupos experimentais. No grupo P, os animais diabéticos foram utilizados para caracterização da dose-resposta da Insulina Degludeca sobre a glicemia. Os sete grupos experimentais foram distribuídos em: Grupo controle (C), diabético (D), diabético com GLN (DG), diabético com Insulina Degludeca (DIT), diabético com Insulina Degludeca e GLN (DITG), diabético com Insulina Regular (DIR) e diabético com Insulina Regular e GLN (DIRG). Os animais receberam suplementação oral diária durante 30 dias com solução salina 0,9% ou GLN 400 mg/Kg e, também, injeção subcutânea de solução salina 0,9% ou Insulina Degludeca (5,0 U/Kg), ou ainda injeção intraperitoneal de Insulina Regular (1,0 U/Kg). Durante o tratamento, a glicemia em jejum e pós-prandial, ingestão alimentar e massa corporal foram avaliadas semanalmente. Passado o período de tratamento, os animais foram submetidos a eutanásia por sobredose anestésica e amostras de sangue foram coletadas, via punção cardíaca, para dosagem de glicose, frutosamina, alanina aminotransferase (ALT), aspartato aminotransferase (AST), proteínas totais, ureia e amônia, avaliação da capacidade antioxidante total (TAC) e avalição de parâmetros bioquímicos relacionados ao perfil lipídico. Ainda, o fígado foi coletado e amostras foram processadas para análise morfológica e histoquímica. Em cortes corados em Hematoxilina-Eosina avaliou-se o número e área de hepatócitos e, em cortes corados com Ácido Periódico de Schiff, avaliou-se o percentual de glicogênio intracelular. Amostras de fígado também foram utilizadas para avaliação do estresse oxidativo hepático. Uma alíquota de fígado homogeneizado com tampão fosfato de potássio 0,1 M (pH 7,4) foi utilizado para determinar o conteúdo de glutationa oxidada (GSSG) e reduzida (GSH) em espectrofluorímetro. O homogenato remanescente foi centrifugado e o sobrenadante utilizado para determinar a atividade das enzimas antioxidantes catalase (CAT) e superóxido dismutase (SOD) e os níveis das proteínas carboniladas em espectrofotômetro. Para análise do metabolismo hepático de glicose, animais em jejum foram anestesiados e submetidos à técnica de perfusão com colagenase 3%; os hepatócitos isolados foram incubados durante 1 hora na ausência ou presença dos agentes glicogenolíticos glucagon, cortisol, adrenalina, isoproterenol (agonista ?-adrenérgico), e dos substratos gliconeogênicos como o glicerol, L-lactato, L-alanina ou L-glutamina. Por fim, após centrifugação, os líquidos de incubação foram utilizados para determinação da glicose e L-lactato. Os resultados foram apresentados como média ± erro padrão. A determinação da dose de Insulina Degludeca foi feita por teste 't' de Student. Os dados paramétricos foram comparados por análise de variância (ANOVA) e pós-teste de Tukey. Os dados não-paramétricos foram comparados por análise de Kruskal-Wallis e pós-teste de Dunns, p<0,05. A dose de 5,0 U/Kg da Insulina Degludeca promoveu redução (p<0,05) da glicemia no estado alimentado (8h, 3º dia) e após jejum noturno (8h, 4º dia) e, dessa forma, foi a dose escolhida para o tratamento nos grupos DIT e DITG. T1DM promoveu aumento das glicemias de jejum e pós-prandial e perda de massa corporal, o que são características da doença. A reposição hormonal com a Insulina Degludeca (DIT) foi eficaz em diminuir a glicemia de jejum com 30 dias de tratamento, embora sem alcançar os valores do grupo C. Já a perda de massa corporal foi menor nos grupos tratados com ambas insulinas (DIT e DIR), sendo que GLN interferiu nesse parâmetro quando associado a Insulina Regular (DIRG). As diferenças entre as cinéticas de liberação das insulinas do tecido subcutâneo para a corrente sanguínea, pode ter sido responsável pelos efeitos fisiológicos observados. A ausência de insulina em T1DM promove alterações na lipólise, proteólise e injuria tecidual associada a hiperglicemia. A produção excessiva de triglicerídeos em T1DM, foi aumentada pela Insulina Degludeca, o que pode estar associada a redução da glicemia de jejum via aumento da lipogênese de novo hepática a partir da glicose circulante. Além disso, a ausência de alterações no padrão de ingestão alimentar associado à redução da perda de massa corporal podem indicar um efeito diferenciado desta insulina sobre a regulação da lipólise e do nível de degradação proteica. A Insulina Regular também promoveu um aumento dos triglicerídeos, todavia, este aumento foi 50% menor comparado a DIT. A associação de GLN aos grupos tratados com ambas insulinas parece atenuar os efeitos do diabetes no que diz respeito ao perfil lipídico. Os grupos tratados com Degludeca (DIT e DITG) foram capazes de aumentar a concentração de proteínas totais e diminuir as dosagens de ureia em relação ao grupo diabético D, o que indica um efeito positivo dessa insulina sobre esse aspecto e pode estar relacionado com a menor degradação proteica e preservação de massa corporal observado nesses grupos. A GLN isolada, ou associada a Insulina Regular, não interferiu nesses parâmetros, demonstrando um efeito de Degludeca per se. Embora GLN (DG) não tenha alterado as dosagens de frutosamina, aumentou em 2 vezes os valores de AST e ALT, o que necessita de maiores investigações. A adição de GLN a Insulina Regular também aumentou as dosagens das transaminases a valores excessivos, o que poderia indicar a influência desse aminoácido sobre a expressão de determinadas proteínas e vias metabólicas, que influenciariam o acúmulo de lipídios ou a inflamação. Por outro lado, o tratamento com Degludeca reduziu todos esses parâmetros. Ambas insulinas promoveram aumento de CAT e SOD e diminuição das proteínas carboniladas. No entanto, a adição de GLN à Insulina Regular promoveu aumento nos níveis de GSH, GSH+GSSG e GSH/GSSG. Todos os grupos diabéticos apresentaram aumento da área dos hepatócitos, no entanto, somente em DIT isto foi acompanhado de maior acúmulo de glicogênio. A adição de GLN (DITG) promoveu diminuição desse acúmulo e da área, e restaurou o número de hepatócitos, diminuído em DIT. Dessa forma, a redução dos triglicerídeos e do conteúdo de glicogênio em DITG podem ser responsáveis pela falta de efeitos sobre a glicemia de jejum. Na ausência (basal) e presença de todos os precursores gliconeogênicos utilizados, T1DM promoveu diminuição da capacidade gliconeogênica, o que pode ser devido a um desvio da glicose para síntese indireta de glicogênio. Dessa forma, o acúmulo de glicogênio encontrado pode ser resultado tanto da síntese de glicogênio, como da hiperglicemia e da deterioração do sistema contrarregulador da glicemia. Para todos os precursores gliconeogênicos testados, o aumento da produção de glicose observado em DIT, pode ser um dos fatores responsáveis pelo maior acúmulo de glicogênio e hipertrigliceridemia via lipogênese de novo (LDN) a partir do excedente de glicose. A associação com GLN (DITG) reverte ambos parâmetros, que pode ser devido a redução da gliconeogênese. Ambas as insulinas aumentam a capacidade e a intensidade da resposta glicogenolítica. Esse efeito foi compartilhado pela GLN isolada (DG), indicando um efeito da GLN per se, e não da associação sobre este parâmetro. Por outro lado, a GLN, isolada e associada as insulinas, aproxima os valores ?-adrenérgicos dos valores do grupo D, não promovendo a melhora esperada. A associação das insulinas com GLN também resultou em alterações contrárias na produção de L-lactato, basal e estimulado, resultando em aumento em DITG e diminuição em DIRG. Isso pode ter ocorrido devido a alteração no potencial redox, sem interferir com a gliconeogênese. Os tratamentos não alteraram a produção de L-lactato a partir da L-alanina, mas aumentaram a produção de glicose. De modo geral, na presença de glicerol e L-glutamina, a produção de L-lactato aumentou nos grupos tratados, mesmo o L-lactato não sendo produto direto desses precursores, o que pode indicar que estes tenham tornado o ambiente celular reduzido. A associação de GLN com as insulinas atenua os efeitos do diabetes sobre o perfil lipídico e conteúdo de glicogênio hepático. A produção exacerbada de VLDL e triglicerídeos, e o elevado estoque de glicogênio, podem estar associados a redução da glicemia de jejum, com 30 dias de tratamento com Degludeca. A elevada gliconeogênese hepática sugere que o mecanismo seja via lipogênese de novo. A GLN associada a Degludeca normaliza as transaminases plasmáticas, mas somente GLN associada a Insulina Regular modifica a glutationa do sangue. Pelo fato dos diferentes tipos de Insulina apresentarem perfis regulatórios diferenciados e a GLN modificar a ação insulínica, a utilização da GLN não deve ser indiscriminada em estados catabólicosAbstract: Type 1 diabetes mellitus (T1DM) is a chronic disease resulting from the immune destruction of ?-pancreatic cells, which leads to loss of endogenous insulin secretion. The inability of insulin-dependent tissues to collect glucose leads to dysregulation of hepatic glucose metabolism which results in hyperglycemia. Several types of insulin are used in the compulsory hormone replacement of T1DM patients, ranging from ultrafast, fast, intermediate and long-term. On the other hand, the amino acid L-glutamine (GLN) has the ability to reduce oxidative stress and chronic complications associated with T1DM, however, its plasma concentration are generally decreased in these patients. This opens the possibility of GLN supplementation concomitant with hormone replacement with insulin. Evaluate the effects of hormone replacement with Degludeca Insulin (long duration - basal) or Regular Insulin (rapid duration), associated or not with oral supplementation with GLN, on physiological and plasma parameters, oxidative stress, liver metabolism and liver histological characteristics of Wistar T1DM rats. Male Wistar rats (50 days old) were divided into one standardization group (P) and seven experimental groups. In P group, diabetic animals were used to characterize the dose response of Degludeca insulin on blood glucose. The seven experimental groups were divided into: Control group (C), diabetic (D), diabetic with GLN (DG), diabetic with Degludeca insulin (DIT), diabetic with Degludeca insulin and GLN (DITG), diabetic with Regular Insulin (DIR) ) and diabetic with Regular Insulin and GLN (DIRG). The animals received daily oral supplementation for 30 days with 0.9% saline or GLN 400 mg / kg and also subcutaneous injection of 0.9% saline or Degludeca Insulin (5.0 U / Kg), or intraperitoneal injection of Regular Insulin (1.0 U / kg). During treatment, fasting and postprandial blood glucose, food intake and body mass was assessed weekly. After the treatment period, the animals was euthanized by anesthetic overdose and blood samples were collected via cardiac puncture for glucose, fructosamine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein, urea and ammonia, evaluation of total antioxidant capacity (TAC) and evaluation of biochemical parameters related to lipid profile. In addition, the liver was collected and samples was processed for morphological and histochemical analysis. In hematoxylin-eosin stained sections, the number and area of hepatocytes were evaluated, and in sections stained with Schiff Periodic Acid, the percentage of intracellular glycogen was evaluated. Liver samples were also used for evaluation of hepatic oxidative stress. An aliquot of liver homogenized with 0.1 M potassium phosphate buffer (pH 7.4) was used to determine the oxidized (GSSG) and reduced (GSH) glutathione content in spectrofluorimeter. The remaining homogenate was centrifuged and the supernatant used to determine the activity of catalase (CAT) and superoxide dismutase (SOD) antioxidant enzymes and carbonylated protein levels in spectrophotometer. For analysis of hepatic glucose metabolism, fasting animals were anesthetized and submitted to the 3% collagenase perfusion technique; isolated hepatocytes were incubated for 1 hour in the absence or presence of glycogenolytic agents glucagon, cortisol, adrenaline, isoproterenol (?-adrenergic agonist), or gluconeogenic substrates such as glycerol, L-lactate, L-alanine or L-glutamine. Finally, after centrifugation, incubation fluids were used to determine glucose and L-lactate. Results were presented as mean ± standard error. Parametric data were compared by analysis of variance (ANOVA) and Tukey post-test. Nonparametric data were compared by Kruskal-Wallis analysis and Dunns post-test, p <0.05. The 5.0 U / kg dose of Degludec Insulin caused a reduction (p <0.05) of blood glucose in the fed state (8h, 3rd day) and after night fasting (8h, 4th day) and was the dose chosen for treatment in the DIT and DITG groups. T1DM promoted increase in fasting and postprandial blood glucose levels and loss of body mass, which are characteristic of the disease. Hormone replacement with Degludec Insulin (DIT) was effective in decreasing fasting blood glucose after 30 days of treatment, although without reaching the values of group C. The loss of body mass was lower in the groups treated with both insulins (DIT and DIR), and GLN interfered with this parameter when associated with Regular Insulin (DIRG). The differences between the kinetics releases of insulins from subcutaneous tissue to the bloodstream may have been responsible for the observed physiological effects. Absence of insulin in T1DM promotes changes in lipolysis, proteolysis and tissue injury associated with hyperglycemia. Degludec Insulin increased excessive triglyceride production in T1DM, which may be associated with reduced fasting glucose via increased new hepatic lipogenesis from circulating glucose. In addition, the absence of changes in dietary intake pattern associated with reduced body mass loss may indicate a differentiated effect of this insulin on the regulation of lipolysis and the level of protein degradation. Regular Insulin promoted an increase in triglycerides, however, this increase was 50% lower compared to DIT. The association of GLN with the groups treated with both insulins seems to attenuate the effects of diabetes regarding the lipid profile. Degludec treated groups (DIT and DITG) were able to increase total protein concentration and decrease urea dosages compared to diabetic group D which indicates a positive effect of this insulin on this aspect and may be related to lower protein degradation and preservation of body mass observed in these groups. GLN alone or associated with Regular Insulin did'n interfere with these parameters, demonstrating an effect of Degludec per se. Although GLN (DG) did'n change the fructosamine dosages and increased in 2 times the AST and ALT values which needs further investigation. The addition of GLN to Regular Insulin also increased transaminase dosages to excessive values which could indicate the influence of this amino acid on the expression of certain proteins and metabolic pathways that would influence lipid accumulation or inflammation. On the other hand, treatment with Degludec reduced all these parameters. Both insulins promoted increase of CAT and SOD and decrease of carbonylated proteins. However, the addition of GLN to Regular Insulin promoted increase in GSH, GSH + GSSG and GSH / GSSG levels. All diabetic groups showed increase hepatocyte area; however, only in DIT this was accompanied by higher glycogen accumulation. The addition of GLN (DITG) promoted decrease of this accumulation and area, and restored the number of hepatocytes, decreased in DIT. Therefore, the reduction in triglycerides and glycogen content in DITG may be responsible for the lack of effects on fasting glucose. In the absence (basal) and presence of all gluconeogenic precursors used, T1DM promoted decrease in gluconeogenic capacity, which may be due to a deviation of glucose for indirect glycogen synthesis. Thus, the accumulation of glycogen may be the result of both glycogen synthesis, hyperglycemia and deterioration of the glycemic counterregulatory system. For all gluconeogenic precursors tested, the increase glucose production observed in DIT may be one of the factors responsible for the higher glycogen accumulation and hypertriglyceridemia via de novo lipogenesis (LDN) from glucose surplus. The association with GLN (DITG) reverse both parameters, which may be due to reduced gluconeogenesis. Both insulins increase the capacity and intensity of the glycogenolytic response. This effect was shared by GLN alone (DG), indicating an effect of GLN per se rather than the association on this parameter. On the other hand, GLN isolated and associated with insulins approximates the ?-adrenergic values to those of group D, not promoting the expected improvement. The association of insulin with GLN also resulted in contrary changes in basal and stimulated L-lactate production, resulting in increase in DITG and decrease in DIRG. This may have occurred to a change in redox potential without interfering with gluconeogenesis. The treatments did'n alter L-lactate production from L-alanine, but increased glucose production. In general, in the presence of glycerol and L-glutamine, L-lactate production increased in the treated groups, even though L-lactate was not a direct product of these precursors which may indicate that they have reduced the cellular environment. The association of GLN with insulins attenuate the effects of diabetes on lipid profile and hepatic glycogen content. Exacerbated production of VLDL and triglycerides, and high glycogen stores may be associated with reduced fasting glucose with 30 days of treatment with Degludec. The elevated hepatic gluconeogenesis suggest that the mechanism is via de novo lipogenesis. GLN associated with Degludec Insulin normalize plasma transaminases but only GLN associated with Regular Insulin modifies blood glutathione. Because different types of insulin have different regulatory profiles and GLN modifies insulin action, the use of GLN shouldn't be indiscriminate in catabolic patient

Assessment of intrinsic capacity in the Brazilian older population and the psychometric properties of the WHO/ICOPE screening tool: a multicenter cohort study protocol

INTRODUCTION: The World Health Organization (WHO) has proposed to monitor intrinsic capacity (IC) in the older population as a public health strategy through the Integrated Care for Older People (ICOPE) program. Although the program has been developed based on solid concepts, scientific evidence on its practical applicability is still scarce. OBJECTIVES: To evaluate IC in Brazilian older adults, its progress over time, and its association with sociodemographic and health factors and outcomes. To evaluate the psychometric properties of the WHO/ICOPE screening tool. METHODS: This is a prospective multicenter cohort study with a 36-month follow-up. We will recruit 3838 people aged &ge; 60 years, registered in the health care units included in the study by the participating centers. We will collect sociodemographic and health data and will administer tools to assess IC domains, both those provided for in the ICOPE screening tool and the sequence of confirmatory assessments provided for in the program. Participants will be reassessed every 6 months for 36 months. EXPECTED RESULTS: To establish the profile of IC in the study population and to understand its progress and the variables associated with the clinical outcomes of interest. To reveal the diagnostic and psychometric properties of the WHO/ICOPE screening tool. The project is funded by the Brazilian National Council for Scientific and Technological Development (CNPq). RELEVANCE: Understanding the potential use of the ICOPE public health strategy proposed by the WHO within the scope of the Brazilian Unified Health System (SUS) by integrating several research centers in the field of Geriatrics and Gerontology throughout Brazil.</p