Is Macronutrients Intake a Challenge for Cardiometabolic Risk in Obese Adolescents?

(1) Background: Pediatric obesity is an emerging public health issue, mainly related to western diet. A cross-sectional study was conducted to explore the association between macronutrients intake and cardiometabolic risk factors in obese adolescents. (2) Methods: Ninety-three Italian obese adolescents were recruited; anthropometric parameters, body composition, glucose and lipid metabolism profiles were measured. Macronutrients intake was estimated by a software-assisted analysis of a 120-item frequency questionnaire. The association between macronutrients and cardiometabolic risk factors was assessed by bivariate correlation, and multiple regression analysis was used to adjust for confounders such as age and sex. (3) Results: By multiple regression analysis, we found that higher energy and lower carbohydrate intakes predicted higher body mass index (BMI) z-score, p = 0.005, and higher saturated fats intake and higher age predicted higher HOmeostasis Model Assessment of insulin resistance (HOMA-IR) and lower QUantitative Insulin-sensitivity ChecK (QUICK) index, p = 0.001. In addition, a saturated fats intake <7% was associated with normal HOMA-IR, and a higher total fats intake predicted a higher HOMA of percent \u3b2-cell function (HOMA-\u3b2), p = 0.011. (4) Conclusions: Higher energy intake and lower carbohydrate dietary intake predicted higher BMI z-score after adjustment for age and sex. Higher total and saturated fats dietary intakes predicted insulin resistance, even after adjustment for confounding factors. A dietary pattern including appropriate high-quality carbohydrate and reduced saturated fat intakes could result in reduced cardiometabolic risk in obese adolescents

Permeability of self-affine rough fractures

The permeability of two-dimensional fractures with self-affine fractal roughness is studied via analytic arguments and numerical simulations. The limit where the roughness amplitude is small compared with average fracture aperture is analyzed by a perturbation method, while in the opposite case of narrow aperture, we use heuristic arguments based on lubrication theory. Numerical simulations, using the lattice Boltzmann method, are used to examine the complete range of aperture sizes, and confirm the analytic arguments.Comment: 11 pages, 9 figure

Oncogenic Gq/11 signaling acutely drives and chronically sustains metabolic reprogramming in uveal melanoma

Metabolic reprogramming has been shown to occur in uveal melanoma (UM), the most common intraocular tumor in adults. Mechanisms driving metabolic reprogramming in UM are poorly understood. Elucidation of these mechanisms could inform development of new therapeutic strategies for metastatic UM, which has poor prognosis because existing therapies are ineffective. Here, we determined whether metabolic reprogramming is driven by constitutively active mutant α-subunits of the heterotrimeric G proteins Gq or G11 (Gq/11), the oncogenic drivers in ∼90% of UM patients. Using PET-computed tomography imaging, microphysiometry, and GC/MS, we found that inhibition of oncogenic Gq/11 with the small molecule FR900359 (FR) attenuated glucose uptake by UM cells in vivo and in vitro, blunted glycolysis and mitochondrial respiration in UM cell lines and tumor cells isolated from patients, and reduced levels of several glycolytic and tricarboxylic acid cycle intermediates. FR acutely inhibited glycolysis and respiration and chronically attenuated expression of genes in both metabolic processes. UM therefore differs from other melanomas that exhibit a classic Warburg effect. Metabolic reprogramming in UM cell lines and patient samples involved protein kinase C and extracellular signal-regulated protein kinase 1/2 signaling downstream of oncogenic Gq/11. Chronic administration of FR upregulated expression of genes involved in metabolite scavenging and redox homeostasis, potentially as an adaptive mechanism explaining why FR does not efficiently kill UM tumor cells or regress UM tumor xenografts. These results establish that oncogenic Gq/11 signaling is a crucial driver of metabolic reprogramming in UM and lay a foundation for studies aimed at targeting metabolic reprogramming for therapeutic development

Diffusion as mixing mechanism in granular materials

We present several numerical results on granular mixtures. In particular, we examine the efficiency of diffusion as a mixing mechanism in these systems. The collisions are inelastic and to compensate the energy loss, we thermalize the grains by adding a random force. Starting with a segregated system, we show that uniform agitation (heating) leads to a uniform mixture of grains of different sizes. We define a characteristic mixing time, $\tau_{mix}$, and study theoretically and numerically its dependence on other parameters like the density. We examine a model for bidisperse systems for which we can calculate some physical quantities. We also examine the effect of a temperature gradient and demonstrate the appearance of an expected segregation.Comment: 15 eps figures, include

Advances in pre-treatment evaluation of pancreatic ductal adenocarcinoma: a narrative review

Background and Objective: Despite advances in the multidisciplinary management of pancreatic cancer, overall prognosis remains poor, due to early progression of the disease. There is a need to also take action in staging, to make it increasingly accurate and complete, to define the setting of the therapeutic strategy. This review was planned to update the current status of pre-treatment evaluation for pancreatic cancer. Methods: We conducted an extensive review, including relevant articles dealing with traditional imaging, functional imaging and minimally invasive surgical procedures before treatment for pancreatic cancer. We searched articles written in English only. Data in the PubMed database, published in the period between January 2000 and January 2022, were retrieved. Prospective observational studies, retrospective analyses and meta-analyses were reviewed and analysed. Key Content and Findings: Each imaging modality (endoscopic ultrasonography, endoscopic retrograde staging laparoscopy) has its own diagnostic advantages and limitations. The sensitivity, specificity and accuracy for each image set are reported. Data that support the increasing role of neoadjuvant therapy (radiotherapy and chemotherapy) and the meaning of a patient-tailored treatment selection, based on tumour staging, are also discussed. Conclusions: A multimodal pre-treatment workup should be searched as it improves staging accuracy, orienting patients with resectable tumors towards surgery, optimizing patient selection with locally advanced tumors to neoadjuvant or definite therapy and avoiding surgical resection or curative radiotherapy in those with metastatic disease

Dog erythrocyte antigens (DEA) 1, 4, 7 and suspected naturally occurring anti-DEA 7 antibodies in italian corso dogs

We sought to determine the prevalence of dog erythrocyte antigen (DEA) 1, 4 and 7 and naturally occurring anti-DEA7 antibodies in Italian Corso dogs. In addition, we correlated DEAs with different epidemiologic variables, compared the prevalence of DEAs against other canine populations and assessed the risk of sensitisation and transfusion reactions (TRs) following unmatched transfusion. Blood samples from 100 Corso dogs were evaluated for DEA 1, 4, 7 and naturally occurring anti-DEA 7 antibodies. Seventy-one percent of samples were DEA 1-negative, 100% tested DEA 4-positive, and 95% tested DEA 7-negative. Suspected anti-DEA7 antibodies were found in 32% dogs. The DEA 1 and 7-negative phenotypes were significantly more common than in most canine populations. When a previously tested Italian canine population was considered as blood donors for Corso dogs, the risk of DEA 1 sensitisation using DEA 1 untyped blood was 29%, and of acute haemolytic TRs after a second untyped DEA 1-incompatible transfusion was 8%. The potential for delayed TRs between DEA 7-negative Corso dogs with suspected naturally occurring anti-DEA 7 antibodies receiving untyped DEA 7-positive blood was 11%. Conversely, when Corso dogs were blood donors for the same population, the risk of DEA 1 sensitisation was 17% and the risk of an acute haemolytic TR after a second DEA 1-incompatible blood transfusion was 3%. Corso dogs can be suitable blood donors. Additional studies are needed to clarify whether the high prevalence of naturally occurring anti-DEA 7 antibodies in this breed could increase their risk of delayed TRs when they are blood recipients

Energy Dissipation and Trapping of Particles Moving on a Rough Surface

We report an experimental, numerical and theoretical study of the motion of a ball on a rough inclined surface. The control parameters are $D$, the diameter of the ball, $\theta$, the inclination angle of the rough surface and $E_{ki}$, the initial kinetic energy. When the angle of inclination is larger than some critical value, $\theta>\theta_{T}$, the ball moves at a constant average velocity which is independent of the initial conditions. For an angle $\theta < \theta_{T}$, the balls are trapped after moving a certain distance. The dependence of the travelled distances on $E_{ki}$, $D$ and $\theta$. is analysed. The existence of two kinds of mechanisms of dissipation is thus brought to light. We find that for high initial velocities the friction force is constant. As the velocity decreases below a certain threshold the friction becomes viscous.Comment: 8 pages RevTeX, 12 Postscript figure