Towards precision medicine in bariatric surgery prescription

Obesity is a complex, multifactorial and chronic disease. Bariatric surgery is a safe and effective treatment intervention for obesity and obesity-related diseases. However, weight loss after surgery can be highly heterogeneous and is not entirely predictable, particularly in the long-term after intervention. In this review, we present and discuss the available data on patient-related and procedure-related factors that were previously appointed as putative predictors of bariatric surgery outcomes. In addition, we present a critical appraisal of the available evidence on which factors could be taken into account when recommending and deciding which bariatric procedure to perform. Several patient-related features were identified as having a potential impact on weight loss after bariatric surgery, including age, gender, anthropometrics, obesity co-morbidities, eating behavior, genetic background, circulating biomarkers (microRNAs, metabolites and hormones), psychological and socioeconomic factors. However, none of these factors are sufficiently robust to be used as predictive factors. Overall, there is no doubt that before we long for precision medicine, there is the unmet need for a better understanding of the socio-biological drivers of weight gain, weight loss failure and weight-regain after bariatric interventions. Machine learning models targeting preoperative factors and effectiveness measurements of specific bariatric surgery interventions, would enable a more precise identification of the causal links between determinants of weight gain and weight loss. Artificial intelligence algorithms to be used in clinical practice to predict the response to bariatric surgery interventions could then be created, which would ultimately allow to move forward into precision medicine in bariatric surgery prescription

Experimental and Numerical Investigation of Post-Flutter Limit Cycle Oscillations on a Cantilevered Flat Plate

Futuristic aircraft designs and novel aircraft such as High Altitude Long Endurance (HALE) involve a higher level of structural flexibility than in conventional aircraft. Even at present, the trends in the aviation industry are to increase wing length (to reduce induced drag) and maxi- mize use of composites, which lead to increased structural flexibility. This necessitates a rethink of conventional (linear) aeroelastic analysis, since the increased flexibility results in coupling between the flight dynamic and aeroelastic dynamics, and consequently, limit-cycle oscillations of the structure. In this paper, a new three-dimensional low-order model for unsteady aerody- namics that accounts for large oscillation amplitudes and nonplanar wakes is developed. An experiment with a cantilevered flat plate at low Reynolds number is set up and used to validate the low-order model, as well as to study post-flutter limit-cycle oscillations. Results from the low-order model are promising, but show that aerodynamic nonlinearities such as flow sepa- ration and leading-edge vortex shedding must also be modeled in order to predict all possible limit-cycle oscillations of the aeroelastic system

Renal Dysfunction Phenotypes in Patients Undergoing Obesity Surgery

Obesity surgery candidates are at an increased risk of kidney injury, but pre-operative evaluation usually neglects kidney function assessment. This study aimed to identify renal dysfunction in candidates for bariatric surgery. To reduce the sources of bias, subjects with diabetes, prediabetes under metformin treatment, neoplastic or inflammatory diseases were excluded. Patients' (n = 192) average body mass index was 41.7 +/- 5.4 kg/m(2). Among these, 51% (n = 94) had creatinine clearance over 140 mL/min, 22.4% (n = 43) had proteinuria over 150 mg/day and 14.6% (n = 28) albuminuria over 30 mg/day. A creatinine clearance higher than 140 mL/min was associated with higher levels of proteinuria and albuminuria. Univariate analysis identified sex, glycated hemoglobin, uric acid, HDL and VLDL cholesterol as being associated with albuminuria, but not with proteinuria. On multivariate analysis, glycated hemoglobin and creatinine clearance as continuous variables were significantly associated with albuminuria. In summary, in our patient population prediabetes, lipid abnormalities and hyperuricemia were associated with albuminuria, but not with proteinuria, suggesting different disease mechanisms might be implicated. Data suggest that in obesity-associated kidney disease, tubulointerstitial injury precedes glomerulopathy. A significant proportion of obesity surgery candidates present clinically relevant albuminuria and proteinuria along with renal hyperfiltration, suggesting that routine pre-operative assessment of these parameters should be considered

Accuracy of prediction models for long-term type 2 diabetes remission after gastric bypass

AimTo evaluate the accuracy of DiaBetter, DiaRem, Ad-DiaRem and 5y-Ad-DiaRem scores' at predicting T2D remission 10 or more years after surgery.MethodsPatients with obesity and T2D (n = 126) submitted to RYGB with 10 or more years of follow-up. It was a unicentric trial. Pre-operative anthropometric and clinical data was retrieved to calculate DiaRem, DiaBetter, Ad-DiaRem and 5y-Ad-DiaRem scores, while a hospital visit was conducted to assess current diabetes status. The area under the receiver operating characteristic (AUROC) curve was calculated as estimate of the scores' accuracy to predict long-term T2D remission.ResultsAmong the entire cohort (n = 126), 70 subjects (55.6%) achieved and maintained T2D remission 10 or more years after RYGB. The 5y-Ad-DiaRem score was the one that depicted the highest discriminative power (AUROC = 0.838) to predict long-term T2D remission when compared to DiaBetter (AUROC = 0.735), DiaRem (AUROC = 0.721) and Ad-DiaRem (AUROC = 0.720).ConclusionThe score with highest accuracy to predict long-term T2D remission after RYGB surgery was the 5y-Ad-DiaRem. Yet, the available scores accuracy to predict T2D remission in the long term is still suboptimal, highlighting the unmet need for a better scoring system

GLP-1 Increases Circulating Leptin Levels in Truncal Vagotomized Rats

GLP-1 is a gastro-intestinal hormone acting within the gut/brain axis for energy balance regulation. We aimed to evaluate the role of the vagus nerve in whole-body energy homeostasis and in mediating GLP-1 effects. For this, rats submitted to truncal vagotomy and sham-operated controls underwent a comprehensive evaluation, including eating behavior, body weight, percentage of white (WAT) and brown adipose tissue (BAT), resting energy expenditure (REE) and acute response to GLP-1. Truncal vagotomized rats had significantly lower food intake, body weight, body weight gain, WAT and BAT, with a higher BAT/WAT ratio, but no significant difference in REE when compared to controls. Vagotomized rats also had significantly higher fasting ghrelin and lower glucose and insulin levels. After GLP-1 administration, vagotomized rats depicted a blunted anorexigenic response and higher plasma leptin levels, as compared to controls. However, in vitro stimulation of VAT explants with GLP-1 resulted in no significant changes in leptin secretion. In conclusion, the vagus nerve influences whole-body energy homeostasis by modifying food intake, body weight and body composition and by mediating the GLP-1 anorectic response. The higher leptin levels in response to acute GLP-1 administration observed after truncal vagotomy suggest the existence of a putative GLP-1-leptin axis that relies on the integrity of gut-brain vagal pathway

Visceral Adipose Tissue Bioenergetics Varies According to Individuals' Obesity Class

Obesity is associated with complex adipose tissue energy metabolism remodeling. Whether AT metabolic reprogramming differs according to body mass index (BMI) and across different obesity classes is unknown. This study's purpose was to evaluate and compare bioenergetics and energy substrate preference of visceral adipose tissue (VAT) pertaining to individuals with obesity class 2 and class 3. VAT obtained from patients with obesity (n = 15) class 2 (n = 7; BMI 37.53 +/- 0.58 kg/m(2)) or class 3 (n = 8; BMI 47.79 +/- 1.52 kg/m(2)) was used to assess oxygen consumption rate (OCR) bioenergetics and mitochondrial substrate preferences. VAT of patients with obesity class 3 presented significantly higher non-mitochondrial oxygen consumption (p < 0.05). In VAT of patients with obesity class 2, inhibition of pyruvate and glutamine metabolism significantly decreased maximal respiration and spare respiratory capacity (p < 0.05), while pyruvate and fatty acid metabolism inhibition, which renders glutamine the only available substrate, increased the proton leak with a protective role against oxidative stress (p < 0.05). In conclusion, VAT bioenergetics of patients with obesity class 2 depicts a greater dependence on glucose/pyruvate and glutamine metabolism, suggesting that patients within this BMI range are more likely to be responsive to interventions based on energetic substrate modulation for obesity treatment

Numerical study of oil spill in the Patos lagoon under flood and ebb conditions

Facing great obstacles to eradicate environmental hazards generated by oil spills, it is crucial to establish actions against such accidents. In this context, the focus of this study is to analyze oil spills at the harbor region of Rio Grande, Rio Grande do Sul. The Easy Coupling Oil System (ECOS) model was used to model the oil spills under different environmental conditions simulated by the hydrodynamic model Telemac-3D, with the intention to identify the main forces controlling the movement of the oil slicks over a year of averaged hydrodynamic conditions from 2003 to 2015. The computational domain comprises the Patos Lagoon, the harbor area of Rio Grande and the Southern Brazilian Shelf. For the oil spill simulations, eight distinct events were defined considering both flood and ebb conditions in the estuarine region of the Patos Lagoon. The oil spill simulations showed that, in ebb conditions, the oil slick movement is mainly ruled by the currents, moving towards the outflow. After a few hours, the wind action makes the slick move towards the margins of the waterway. In flood conditions, on the other hand, the oil slick drifts to the interior of the estuary, following the dominant currents and the local winds

INCIDENCIA Y PREVALENCIA DE CASOS NOTIFICADOS DE COVID-19 EN EL MUNICIPIO DE PATOS DE MINAS - MG ENTRE LOS MESES DE ABRIL 2020 A ABRIL 2021

O presente estudo objetivou avaliar a incidência e a prevalência dos casos de Covid-19 (infecção por Sars-Cov-2) no município de Patos de Minas – MG. Trata-se de uma pesquisa epidemiológica, observacional, descritiva e ecológica dos dados públicos relativos à esta doença, fornecidos pela secretaria de saúde do município. A análise estatística foi descritiva por meio da determinação das frequências absolutas e relativas dos casos confirmados e notificados de Covid-19 de pacientes que sobreviveram ou vieram à óbito associado a doença em relação ao sexo e à faixa etária. Foram notificados 13.177casos da doença com 423 óbitos. A taxa de letalidade foi de 3,21%. A coleta de dados foi realizada no período de abril de 2020 até maio 2021. Obteve-se uma maior prevalência de casos confirmados entre indivíduos do sexo feminino (n=7.126, 54,1%) e maior prevalência de óbitos entre a população masculina (n=226, 53,42%). A maior incidência dos casos notificados e dos óbitos ocorreram nos meses de julho de 2020 e fevereiro de 2021. Conclui-se que a taxa de letalidade associada à covid-19 no município foi baixa, apresentando maiores incidências em indivíduos do sexo feminino tiveram maior prevalência de infecção ao passo que indivíduos do sexo masculino tiveram maior prevalência de óbitos. Neste período foram verificados dois picos de distribuição da doença. Ressalta-se a necessidade de estudos epidemiológicos como este a fim de traçar estratégias para enfrentamento desta pandemia.The present study aimed to evaluate the incidence and prevalence of cases of Covid-19 (infection by Sars-Cov-2) in the city of Patos de Minas - MG. This is an epidemiological, observational, descriptive and ecological survey of public data relating to this disease, provided by the municipal health department. Statistical analysis was descriptive by determining the absolute and relative frequencies of confirmed and notified cases of Covid-19 of patients who survived or died associated with the disease in relation to sex and age group. 13,177 cases of the disease were reported, with 423 deaths. The fatality rate was 3.21%. Data collection was carried out from April 2020 to May 2021. There was a higher prevalence of confirmed cases among females (n=7,126, 54.1%) and a higher prevalence of deaths among the male population (n=226, 53.42%). The highest incidence of notified cases and deaths occurred in the months of July 2020 and February 2021. It is concluded that the lethality rate associated with covid-19 in the city was low, with higher incidences in females and had a higher prevalence infection, whereas male individuals had a higher prevalence of deaths. During this period, two peaks of disease distribution were observed. It emphasizes the need for epidemiological studies such as this one in order to outline strategies to face this pandemic.El presente estudio tuvo como objetivo evaluar la incidencia y prevalencia de casos de Covid-19 (infección por Sars-Cov-2) en la ciudad de Patos de Minas - MG. Se trata de una encuesta epidemiológica, observacional, descriptiva y ecológica de datos públicos relacionados con esta enfermedad, proporcionada por el departamento de salud municipal. El análisis estadístico fue descriptivo al determinar las frecuencias absolutas y relativas de casos confirmados y notificados de Covid-19 de pacientes que sobrevivieron o fallecieron asociados a la enfermedad en relación al sexo y grupo de edad. Se notificaron 13.177 casos de la enfermedad, con 423 defunciones. La tasa de letalidad fue del 3,21%. La recolección de datos se realizó de abril de 2020 a mayo de 2021. Hubo una mayor prevalencia de casos confirmados entre las mujeres (n = 7.126, 54,1%) y una mayor prevalencia de muertes entre la población masculina (n = 226, 53,42%). La mayor incidencia de casos notificados y defunciones ocurrió en los meses de julio de 2020 y febrero de 2021. Se concluye que la tasa de letalidad asociada al covid-19 en la ciudad fue baja, con mayor incidencia en mujeres y tuvo mayor prevalencia de infección, mientras que los hombres tuvieron una mayor prevalencia de muertes. Durante este período, se observaron dos picos de distribución de la enfermedad. Se enfatiza la necesidad de estudios epidemiológicos como este para delinear estrategias para enfrentar esta pandemia