CVOT summit report 2023: new cardiovascular, kidney, and metabolic outcomes

The 9th Cardiovascular Outcome Trial (CVOT) Summit: Congress on Cardiovascular, Kidney, and Metabolic Outcomes was held virtually on November 30-December 1, 2023. This reference congress served as a platform for in-depth discussions and exchange on recently completed outcomes trials including dapagliflozin (DAPA-MI), semaglutide (SELECT and STEP-HFpEF) and bempedoic acid (CLEAR Outcomes), and the advances they represent in reducing the risk of major adverse cardiovascular events (MACE), improving metabolic outcomes, and treating obesity-related heart failure with preserved ejection fraction (HFpEF). A broad audience of endocrinologists, diabetologists, cardiologists, nephrologists and primary care physicians participated in online discussions on guideline updates for the management of cardiovascular disease (CVD) in diabetes, heart failure (HF) and chronic kidney disease (CKD); advances in the management of type 1 diabetes (T1D) and its comorbidities; advances in the management of CKD with SGLT2 inhibitors and non-steroidal mineralocorticoid receptor antagonists (nsMRAs); and advances in the treatment of obesity with GLP-1 and dual GIP/GLP-1 receptor agonists. The association of diabetes and obesity with nonalcoholic steatohepatitis (NASH; metabolic dysfunction-associated steatohepatitis, MASH) and cancer and possible treatments for these complications were also explored. It is generally assumed that treatment of chronic diseases is equally effective for all patients. However, as discussed at the Summit, this assumption may not be true. Therefore, it is important to enroll patients from diverse racial and ethnic groups in clinical trials and to analyze patient-reported outcomes to assess treatment efficacy, and to develop innovative approaches to tailor medications to those who benefit most with minimal side effects. Other keys to a successful management of diabetes and comorbidities, including dementia, entail the use of continuous glucose monitoring (CGM) technology and the implementation of appropriate patient-physician communication strategies. The 10th Cardiovascular Outcome Trial Summit will be held virtually on December 5–6, 2024 (http://www.cvot.org)

Subcortical volumes across the lifespan: data from 18,605 healthy individuals aged 3-90 years

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.Education and Child Studie

Discrimination between Paralogs using Microarray Analysis: Application to the Yap1p and Yap2p Transcriptional Networks

Ohno [Ohno, S. (1970) in Evolution by Gene Duplication, Springer, New York] proposed that gene duplication with subsequent divergence of paralogs could be a major force in the evolution of new gene functions. In practice the functional differences between closely related homologues produced by duplications can be subtle and difficult to separate experimentally. Here we show that DNA microarrays can distinguish the functions of two closely related homologues from the yeast Saccharomyces cerevisiae, Yap1p and Yap2p. Although Yap1p and Yap2p are both bZIP transcription factors involved in multiple stress responses and are 88% identical in their DNA binding domains, our work shows that these proteins activate nonoverlapping sets of genes. Yap1p controls a set of genes involved in detoxifying the effects of reactive oxygen species, whereas Yap2p controls a set of genes over represented for the function of stabilizing proteins. In addition we show that the binding sites in the promoters of the Yap1p-dependent genes differ from the sites in the promoters of Yap2p-dependent genes and we validate experimentally that these differences are important for regulation by Yap1p. We conclude that while Yap1p and Yap2p may have some overlapping functions they are clearly not redundant and, more generally, that DNA microarray analysis will be an important tool for distinguishing the functions of the large numbers of highly conserved genes found in all eukaryotic genomes

Desempenho e Características da Carcaça de Vacas de Diferentes Grupos Genéticos em Pastagem Cultivada com Suplementação Energética Performance and Carcass Characteristics of Cows of Different Genetic Groups, Submitted to Energetic Supplementation Levels on Winter Cultivated Pasture

O objetivo deste trabalho foi testar diferentes níveis de suplementação energética na forma de grão de sorgo moído, para a terminação em pastagem, de vacas de descarte de diferentes genótipos Charolês (C) x Nelore (N). Foram utilizadas trinta vacas de descarte, dos seguintes grupos genéticos: C, N, 3/4 C + 1/4 N (CN) e 3/4 N + 1/4 C (NC), terminadas em pastagem cultivada de aveia (Avena strigosa) + azevém (Lolium multiflorum), distribuídas em três níveis de suplementação (NS): 0,0; 0,4; ou 0,8% do peso vivo. No estudo do efeito de grupo genético, verificou-se que os ganhos de peso médio diário foram de 1,03; 1,06; 1,36; e 1,02 kg, respectivamente, para C, N, CN e NC. O peso final foi de 453, 412, 515 e 478 kg, citados na mesma ordem. O ganho de condição corporal (CC) durante a terminação foi maior nas vacas N (1,81 pontos) em relação as C (1,09 pontos) e CN (0,99 pontos), ficando as vacas NC com valor intermediário (1,42 pontos). Verificou-se que vacas C apresentam maior peso de carcaça, melhor conformação e área de Longissimus dorsi em relação às vacas N, enquanto estas, apresentam maior percentagem de osso. As vacas CN mostraram carne de coloração mais clara que as NC. Os ganhos de peso médio diário foram de 0,92; 1,23; e 1,20 kg, respectivamente, para os níveis 0,0; 0,4 e 0,8% de suplementação.<br>The objective of this work was to evaluate different levels of enegetic supplementation, in the form of grounded sorghum for finishing of cull cows from different genotypes of Charolais (C) x Nellore (N), kept on cultivated pasture during the last half of the vegetative cycle. Thirty C, N, 3/4 C + 1/4 N (CN) and 3/4 N + 1/4 C (NC) beef cows, kept on cultivated pasture of oats (Avena strigosa) + ryegrass (Lolium multiflorum) were allotted in three supplementation levels: .0, .4 or .8% of live weight. In the study of the genetic group effect, it was observed that the average daily gain was 1.03, 1.06, 1.36 and 1.02 kg, respectively, for C, N, CN and NC. Final live weigth was 453, 412, 515 and 478kg, respectively. The gain in body condition during the finishing was higher for the N cows (1.81 points) than for the C (1.09 points) and CN ( .99 points), while the NC cows showed an intermediate value (1.42 points). Carcasses from C cows showed higher weight, better conformation and Longissimus dorsi area than from the N, while the last ones, showed higher bone percentage in the carcass. Between the crossbreds, the CN meat exhibited brighter color than the NC. With relation to the supplementation level, the average daily gain was .92, 1.23 and 1.20 kg, respectively, for .0, .4 and .8%

Composição física da carcaça, qualidade da carne e conteúdo de colesterol no músculo Longissimus dorsi de novilhos 5/8 Nelore - 3/8 Charolês terminados em confinamento e abatidos em diferentes estádios de maturidade Carcass physical composition, meat quality and cholesterol content in the Longissimus dorsi muscle of 5/8 Nellore - 3/8 Charolais steers feedlot finished and slaughtered at different maturity stages

O experimento foi conduzido com o objetivo de avaliar a composição física da carcaça, a qualidade da carne e o conteúdo de colesterol no músculo Longissimus dorsi de novilhos 5/8 Nelore - 3/8 Charolês terminados em confinamento até atingirem o peso de abate (P) de 425, 467 e 510 kg. Os novilhos apresentaram, ao início do confinamento, idade média de 660 dias, peso de 361 kg e estado corporal de 2,9 pontos. A dieta alimentar, com relação volumoso:concentrado de 60:40, continha 10,25% de proteína bruta, 72,18% de nutrientes digestíveis totais e 3,18 Mcal de energia digestível/kg MS. A quantidade de músculo (<IMG SRC="/img/revistas/rbz/v33n4/22092s1.gif" WIDTH=11 HEIGHT=15 > ou = 15,548+0,316P), gordura (<IMG SRC="/img/revistas/rbz/v33n4/22092s1.gif" WIDTH=11 HEIGHT=15 > ou = -75,971+0,290P) e de gordura interna (<IMG SRC="/img/revistas/rbz/v33n4/22092s1.gif" WIDTH=11 HEIGHT=15 > ou = -61,955+0,178P) da carcaça aumentaram linearmente com o incremento do P. Porém, o percentual de músculo decresceu (<IMG SRC="/img/revistas/rbz/v33n4/22092s1.gif" WIDTH=11 HEIGHT=15 > ou = 90,294-0,059P), o de gordura (<IMG SRC="/img/revistas/rbz/v33n4/22092s1.gif" WIDTH=11 HEIGHT=15 > ou = -5,320+0,060P) aumentou e o de osso permaneceu constante (14,93%) do menor para o maior P. Não houve influência do peso de abate na relação músculo:osso (4,28) e músculo+gordura:osso (5,80). A cor (4,28 pontos) e textura (3,28 pontos) da carne não foram alteradas, porém o marmoreio cresceu linearmente (Ÿ = -8,403+0,035P) com o aumento no P. O peso de abate não influenciou a quebra no processo de descongelamento (11,13%) e de cocção da carne (23,94%). A maciez da carne foi classificada entre "macia e muito macia" (6,77 pontos), a palatabilidade entre "palatável e muito palatável" (6,77 pontos) e a suculência entre "suculenta e muito suculenta" (6,88 pontos), não sendo influenciadas pelo aumento no P. O músculo Longissimus dorsi apresentou 1,63% de extrato etéreo e 53,12 mg de colesterol/100 g de músculo, permanecendo constantes com o aumento do P. Houve correlação positiva do percentual de extrato etéreo do músculo Longissimus dorsi com a espessura de gordura (0,42), o marmoreio (0,46) e o teor de colesterol (0,60).<br>The objective of this experiment was to evaluate the physical carcass composition, meat quality and cholesterol content in the Longissimus dorsi muscle of 5/8 Nellore - 3/8 Charolais steers feedlot finished to reach slaughter weight (SW) of 425, 467 and 510 kg. At the beginning of feedlot, average age, weight and body condition were, respectively, 660 days, 361 kg and 2.9 points. The diet offered, with roughage:concentrate ratio of 60:40, contained 10.25% of crude protein, 72.18% of total digestible nutrients and 3.18 Mcal of digestible energy/kg of DM. The muscle (<IMG SRC="/img/revistas/rbz/v33n4/22092s1.gif" WIDTH=11 HEIGHT=15 > or = 15.548+0.316SW), fat (<IMG SRC="/img/revistas/rbz/v33n4/22092s1.gif" WIDTH=11 HEIGHT=15 > or = -75.971+0.290SW) and internal fat (<IMG SRC="/img/revistas/rbz/v33n4/22092s1.gif" WIDTH=11 HEIGHT=15 > or = -61.955+0.178SW) of the carcass quantity increased linearly as SW increased. However, the muscle percentage declined (<IMG SRC="/img/revistas/rbz/v33n4/22092s1.gif" WIDTH=11 HEIGHT=15 > or = 90.294-0.059PA), the fat percentage increased (<IMG SRC="/img/revistas/rbz/v33n4/22092s1.gif" WIDTH=11 HEIGHT=15 > or = -5.320+0.060PA) and bone percentage was not alterated (14.93%) by SW. The muscle:bone (4.28) and muscle+fat:bone ratio (5.80) was not influenced by SW. The meat color (4.28 points) and texture (3.28 points) were not influenced, however, marbling increased linearly (Ÿ = -8.403+0.035SW) as the SW increased. Slaughter weight did not influence meat thawing (11.13%) and cooking losses (23.94%). The tenderness was classified between "tender and very tender" (6.77 points), palatability between "flavorful and very flavorful " (6.77 points) and juiciness between "juicy and very juicy" (6.88 points), were not influenced by SW. The Longissimus dorsi muscle showed 1.63% of ether extract and 53.12 mg of cholesterol/100 g of muscle, remaining constant with SW increase. Positive correlation of ether extract percentage in the Longissimus dorsi muscle with subcutaneous fat thickness (0.42), with marbling score (0.46) and with cholesterol content (0.60) was observed