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019). No linear association was found between the number of FTO risk allele and the level of serum vitamin D. All patients with high serum level of 25(OH) vitamin D had one or two copies of FTO rs9939609 risk allele. Glutaraldehyde in vitro FTO gene polymorphisms may counteract the beneficial effects of vitamin D in breast cancer prevention. Further studies can help to better understand the genetic factors predisposing to breast cancer and their effect on the association between vitamin D and breast cancer.

Although genetic variants of PNPLA3, TM6SF2 and SAMM50 have been reported to increase the risk of non-alcoholic fatty liver disease (NAFLD), no pediatric studies have evaluated the association between SAMM50 and NAFLD.

This study aimed to investigate the risk factors, including genetic variants, of pediatric NAFLD.

NAFLD was defined as the presence of hepatic steatosis on ultrasound. We included 228 patients with NAFLD (body mass index-Z [BMI-Z]=2.51 ± 1.01) and 225 controls (BMI-Z=0.22 ± 1.48). We genotyped four variants of PNPLA3 (rs738409), TM6SF2 (rs58542926) and SAMM50 (rs2073080 and rs3761472) by TaqMan allelic discrimination. The pediatric NAFLD fibrosis score, aspartate transaminase (AST)/platelet ratio index and fibrosis-4 score were used to evaluate the degree of fibrosis. We calculated the genetic risk score for additive effects according to the sum of risk alleles.

The mean age was 12.6± 3.5 years. The four genetic variants, male sex and BMI-Z, independently increased susceptibility to NAFLD. These four variants, in addition to fasting insulin and triglycerides, remained significant risk factors with higher odds ratios in children with overweight. These variants increased the alanine aminotransferase (ALT) level and three fibrosis scores independently. As the genetic risk score increased, AST, ALT and the fibrosis scores increased independently.

PNPLA3, TM6SF2 and SAMM50 are associated with the development and severity of pediatric NAFLD. The impact of genetic variants is greater in children with overweight. The four genetic variants have synergetic effects on the severity of pediatric NAFLD.

PNPLA3, TM6SF2 and SAMM50 are associated with the development and severity of pediatric NAFLD. The impact of genetic variants is greater in children with overweight. The four genetic variants have synergetic effects on the severity of pediatric NAFLD.Despite profound advances in treatment approaches, gliomas remain associated with very poor prognoses. The residual cells after incomplete resection often migrate and proliferate giving a seed for highly resistant gliomas. The efficacy of chemotherapeutic drugs is often strongly limited by their poor selectivity and the blood brain barrier (BBB). Therefore, the development of therapeutic carrier systems for efficient transport across the BBB and selective delivery to tumor cells remains one of the most complex problems facing molecular medicine and nano-biotechnology. To address this challenge, a stimuli sensitive nanogel is synthesized using pre-polymer approach for the effective delivery of nano-irradiation. The nanogels are cross-linked via matrix metalloproteinase (MMP-2,9) substrate and armed with Auger electron emitting drug 5-[125 I]Iodo-4"-thio-2"-deoxyuridine ([125 I]ITdU) which after release can be incorporated into the DNA of tumor cells. Functionalization with diphtheria toxin receptor ligand allows nanogel transcytosis across the BBB at tumor site. Functionalized nanogels efficiently and increasingly explore transcytosis via BBB co-cultured with glioblastoma cells. The subsequent nanogel degradation correlates with up-regulated MMP2/9. Released [125 I]ITdU follows the thymidine salvage pathway ending in its incorporation into the DNA of tumor cells. With this concept, a highly efficient strategy for intracellular delivery of radiopharmaceuticals across the challenging BBB is presented.

This study examined the associations of Dietary Inflammatory Index (DII) with weight outcomes within 1 year post partum.

This analysis included women who participated in a cohort study in South China (n = 468). The assessments included maternal height, weight, and dietary intake. The latter variable was based on three consecutive 24-hour food records collected at 2 weeks and 1 year after childbirth and was used to calculate the energy-adjusted DII (EDII) scores during and after puerperium, respectively. A general linear regression was performed to examine the relationships between the EDII scores and postpartum weight outcomes after adjusting for confounders.

In an analysis adjusted for confounders, the EDII during puerperium was positively associated with the weight change from 3 to 42 days (β 0.42, 95% CI 0.11-0.70). The EDII after puerperium was positively correlated with the weight changes from 42 days to 1 year (β 0.52, 95% CI 0.02-1.02) and from 3 days to 1 year (β 0.63, 95% CI 0.13-1.14), as well as with the postpartum weight retention at 1 year after childbirth (β 0.75, 95% CI 0.29-1.22).

The results indicate that a diet with a high EDII score might minimize postpartum weight loss and promote higher postpartum weight retention.

The results indicate that a diet with a high EDII score might minimize postpartum weight loss and promote higher postpartum weight retention.The sigma (σ)-hole effect has emerged as a promising tool to construct novel architectures endowed with new properties. A simple yet effective strategy for the generation of monofluoromethyl radical is a continuing challenge within the synthetic community. Flu-oromethylphosphonium salts are easily available, air- and thermally-stable, as well as simple-to-handle. Herein, we report the ability of σ-hole effect to facilitate the visible light-triggered photolysis of phosphonium iodide salts, a charge transfer complex, selectively giving fluoromethyl radicals. The usefulness and versatility of this new protocol are demonstrated through the mono-, di-, and trifluoro-methylation of a variety of alkenes.Glucose-dependent insulinotropic polypeptide (GIP) plays an important role in the glucose and lipid metabolism. We investigated the effects of exogenous GIP on lipid metabolism during time of stable insulin levels. Ten male patients with type 1 diabetes without endogenous insulin secretion (C-peptide-negative, mean [±SD] age 26 ± 4years, body mass index 24 [±2] kg/m2 , glycated haemoglobin 56 [±8] mmol/mol or 7.3 [±0.8]%) were studied in a randomized, double-blind, placebo-controlled, crossover study with continuous intravenous infusions of GIP (4 pmol/kg/min) or placebo (saline), during two separate 90-minute hyperglycaemic (12 mmol/L) clamps with basal insulin substitution (0.1-0.2 mU/kg/min). Plasma glycerol concentrations increased from baseline during GIP infusion and decreased during placebo infusion (baseline-subtracted area under the curve [bsAUC] 703 ± 407 vs. -262 ± 240 μmol/L × min, respectively; P  less then  0.001). Free fatty acids (FFAs) increased during GIP infusions (bsAUC 5505 ± 2170 μEq/L × min) and remained unchanged during placebo infusion (bsAUC -74 ± 2363 μEq/L × min), resulting in a significant difference between GIP and placebo infusions (P  less then  0.001). Plasma concentrations of glucose, insulin, glucagon-like peptide-1 and glucagon were similar during GIP and placebo infusions. GIP increased plasma glycerol and FFAs in patients with type 1 diabetes during hyperglycaemia and stable basal insulin levels. This supports a direct lipolytic effect of GIP at high glucose and low levels of plasma insulin.Endovascular aortic repair (EVAR) has become the preferred intervention option for aortic aneurysms and dissections. This is because EVAR is much less invasive than the alternative open surgery repair. While in hospital mortality rates are smaller for EVAR than open repair (1-2% vs 3-5%), the early benefits of EVAR are lost after 3 years due to larger rates of complications in the EVAR group. Clinicians follow instructions for use (IFU) when possible, but are left with personal experience on how to best proceed and what choices to make with respect to stent graft model choice, sizing, procedural options and their implications on long term outcomes. Computational modeling of stent graft (SG) deployment in EVAR and tissue remodeling after intervention offers an alternative way of testing SG designs in silico, in a personalized way before intervention, to ultimately select the strategies leading to better outcomes. Further, computational modeling can be used in the optimal design of SGs in cases of complex geometries. In this review, we address some of the difficulties and successes associated with computational modeling of EVAR procedures. There is still work to be done in all areas of EVAR in silico modeling, including model validation, before models can be applied in the clinic, but much progress has already been made. Critical to clinical implementation are current efforts focusing on developing fast algorithms that can achieve (near) real time solutions, as well as ways of dealing with inherent uncertainties related to patient aortic wall degradation on an individualized basis. We are optimistic that EVAR modeling in the clinic will soon become a reality to help clinicians optimize EVAR interventions and ultimately reduce EVAR-associated complications. This article is protected by copyright. All rights reserved.

A Mendelian randomization (MR) framework was applied to disentangle the causal effect of branched-chain amino acids (BCAAs) and overweight/obesity in Chinese adolescents.

Circulating BCAA levels were measured by liquid chromatography coupled with mass spectrometry. A total of 7 BCAAs and 12 BMI-associated common variants identified from released genome-wide association study results were genotyped. Furthermore, a bidirectional MR approach was undertaken to disentangle the causal effect of BCAAs and overweight/obesity, using two-stage regression.

Using the inverse variance-weighted strategy and the weighted genetic scoring instruments, the estimated odds ratio per 1-arbitrary-unit increase in the total BCAA level on overweight and obesity odds after adjusting for age and sex was 2.40 (95% CI 1.38 to 3.42, p < 0.001) and 2.55 (95% CI 1.35 to 4.82, p = 0.004), respectively. Furthermore, additional MR tests were undertaken using a reversed model, testing the causal effect of increasing BMI variants on total BCAA level. By contrast, no evidence that increased BMI was causally associated with the total BCAA level (estimated β associated with 1-kg/m

increase in BMI = 0.05, 95% CI -0.17 to 0.28, p = 0.642) was observed.

In summary, BCAAs may be causally associated with overweight/obesity or, rather, a congenital dysmetabolism of BCAAs could be a cause of overweight/obesity in adolescents.

In summary, BCAAs may be causally associated with overweight/obesity or, rather, a congenital dysmetabolism of BCAAs could be a cause of overweight/obesity in adolescents.

Weight-biased attitudes and views held by health care professionals can have a negative impact on the patient-provider relationship and the provision of care, but studies have found mixed results about the extent and nature of bias, which warrants a review of the evidence.

A systematic review and random-effects meta-analysis were conducted by including studies up to January 12, 2021.

A total of 41 studies met inclusion criteria, with 17 studies providing sufficient data to be meta-analyzed. A moderate pooled effect (standardized mean difference = 0.66; 95% CI 0.37-0.96) showed that health care professionals demonstrate implicit weight bias. Health care professionals also report explicit weight bias on the Fat Phobia Scale, Antifat Attitudes Scale, and Attitudes Towards Obese Persons Scale. Findings show that medical doctors, nurses, dietitians, psychologists, physiotherapists, occupational therapists, speech pathologists, podiatrists, and exercise physiologists hold implicit and/or explicit weight-biased attitudes toward people with obesity.