Preclinical studies of166Ho-chitosan for treatment of hepatocellular carcinoma

Introduction: Recently, due to the special characteristics of166Ho and chitosan,166Ho-chitosan complex was developed for treatment of tumors such as hepatocellular carcinoma. This complex has been lately prepared with high radiochemical purity in our lab. The preclinical studies of the complex however should be performed to evaluate the tracer concentration in target and normal tissues before human use. Methods: In this study,166Ho-chitosan was prepared and its preclinical studies for treatment of hepatocellular carcinoma was carried out by injection of the radiopharmaceutical into the rabbit's liver via two different methods, surgery and venography. Leakage of the injected activity from the injection site in the rabbit organs was investigated using SPECT and SPECT-CT imaging up to 24 hours. Results: Both SPECT and SPECT-CT imaging of the rabbits showed that there was no significant leakage of the injected activity. Almost all the activity would remain in the injection site at least 24 h post injection. Conclusion: Considering all of the excellent features of the complex, this radiopharmaceutical is suggestive for treatment of hepatocellular carcinoma by radioembolization method

Age-related decline in antibiotic prescribing for uncomplicated respiratory tract infections in primary care in England following the introduction of a national financial incentive (the Quality Premium) for health commissioners to reduce use of antibiotics in the community: an interrupted time series analysis

Objectives: To assess the impact of the 2015/16 NHS England Quality Premium (which provided a financial incentive for Clinical Commissioning Groups to reduce antibiotic prescribing in primary care) on antibiotic prescribing by General Practitioners (GPs) for respiratory tract infections (RTIs). Method: Interrupted time series analysis using monthly patient-level consultation and prescribing data obtained from the Clinical Practice Research Datalink (CPRD), between April 2011 and March 2017. The study population comprised patients consulting a GP who were diagnosed with an RTI. We assessed the rate of antibiotic prescribing in patients (both aggregate and stratified by age) with a recorded diagnosis of uncomplicated RTI, before and after the implementation of the Quality Premium. Results: Prescribing rates decreased over the six year study period, with evident seasonality. Notably, there was a 3% drop in the rate of antibiotic prescribing (equating to 14.65 prescriptions per 1,000 RTI consultations) (p<0.05) in April 2015, coinciding with the introduction of the Quality Premium. This reduction was sustained, such that after two years there was a 3% decrease in prescribing relative to that expected had the pre-intervention trend continued. There was also a concurrent 2% relative reduction in the rate of broad-spectrum antibiotic prescribing. Antibiotic prescribing for RTIs diagnosed in children showed the greatest decline with a 6% relative change two years after the intervention. Of the RTI indications studied, the greatest reductions in antibiotic prescribing were seen for patients with sore throats. Conclusions: Community prescribing of antibiotics for RTIs significantly decreased following the introduction of the Quality Premium, with the greatest reduction seen in younger patients

Fuzzy uncertainty analysis in the flutter boundary of an aircraft wing subjected to a thrust force

In this study, flutter uncertainty analysis of an aircraft wing subjected to a thrust force is investigated using fuzzy method. The linear wing model contains bending and torsional flexibility and the engine is considered as a rigid external mass with thrust force. Peters’ unsteady thin airfoil theory is used to model the aerodynamic loading. The aeroelastic governing equations are derived based on Hamilton’s principle and converted to a set of ordinary differential equations using Galerkin method. In the flutter analysis, it is assumed that the wing static deflections do not have influence on the results. The wing bending and torsional rigidity, aerodynamic lift curve slope and air density are considered as uncertain parameters and modelled as triangle and trapezium membership functions. The eigenvalue problem with fuzzy input parameters is solved using fuzzy Taylor expansion method and a sensitivity analysis is performed. Also, the upper and lower bounds of flutter region at different α-cuts are extracted. Results show that this method is a low-cost method with reasonable accuracy to estimate the flutter speed and frequency in the presence of uncertainties

Evaluation of the impact of iPSC differentiation protocols on transcriptomic signatures.

Human induced pluripotent stem cells (iPSC) have the potential to produce desired target cell types in vitro and allow for the high-throughput screening of drugs/chemicals at population level thereby minimising the cost of drug discovery and drug withdrawals after clinical trials. There is a substantial need for the characterisation of the iPSC derived models to better understand and utilise them for toxicological relevant applications. In our study, iPSC (SBAD2 or SBAD3 lines obtained from StemBANCC project) were differentiated towards toxicologically relevant cell types: alveolar macrophages, brain capillary endothelial cells, brain cells, endothelial cells, hepatocytes, lung airway epithelium, monocytes, podocytes and renal proximal tubular cells. A targeted transcriptomic approach was employed to understand the effects of differentiation protocols on these cell types. Pearson correlation and principal component analysis (PCA) separated most of the intended target cell types and undifferentiated iPSC models as distinct groups with a high correlation among replicates from the same model. Based on PCA, the intended target cell types could also be separated into the three germ layer groups (ectoderm, endoderm and mesoderm). Differential expression analysis (DESeq2) presented the upregulated genes in each intended target cell types that allowed the evaluation of the differentiation to certain degree and the selection of key differentiation markers. In conclusion, these data confirm the versatile use of iPSC differentiated cell types as standardizable and relevant model systems for in vitro toxicology

The Effect of Dietary Carbohydrate and Fat Manipulation on the Metabolome and Markers of Glucose and Insulin Metabolism: A Randomised Parallel Trial.

From Europe PMC via Jisc Publications RouterHistory: ppub 2022-09-01, epub 2022-09-07Publication status: PublishedHigh carbohydrate, lower fat (HCLF) diets are recommended to reduce cardiometabolic disease (CMD) but low carbohydrate high fat (LCHF) diets can be just as effective. The effect of LCHF on novel insulin resistance biomarkers and the metabolome has not been fully explored. The aim of this study was to investigate the impact of an ad libitum 8-week LCHF diet compared with a HCLF diet on CMD markers, the metabolome, and insulin resistance markers. n = 16 adults were randomly assigned to either LCHF (n = 8, &lt;50 g CHO p/day) or HCLF diet (n = 8) for 8 weeks. At weeks 0, 4 and 8, participants provided fasted blood samples, measures of body composition, blood pressure and dietary intake. Samples were analysed for markers of cardiometabolic disease and underwent non-targeted metabolomic profiling. Both a LCHF and HCLF diet significantly (p &lt; 0.01) improved fasting insulin, HOMA IR, rQUICKI and leptin/adiponectin ratio (p &lt; 0.05) levels. Metabolomic profiling detected 3489 metabolites with 78 metabolites being differentially regulated, for example, an upregulation in lipid metabolites following the LCHF diet may indicate an increase in lipid transport and oxidation, improving insulin sensitivity. In conclusion, both diets may reduce type 2 diabetes risk albeit, a LCHF diet may enhance insulin sensitivity by increasing lipid oxidation

Step-by-step diagnosis and management of the nocebo/drucebo effect in statin-associated muscle symptoms patients: a position paper from the International Lipid Expert Panel (ILEP)

Statin intolerance is a clinical syndrome whereby adverse effects (AEs) associated with statin therapy [most commonly statin-associated muscle symptoms (SAMS)] result in the discontinuation of therapy and consequently increase the risk of adverse cardiovascular outcomes. However, complete statin intolerance occurs in only a small minority of treated patients (estimated prevalence of only 3-5%). Many perceived AEs are misattributed (e.g. physical musculoskeletal injury and inflammatory myopathies), and subjective symptoms occur as a result of the fact that patients expect them to do so when taking medicines (the nocebo/drucebo effect)-what might be truth even for over 50% of all patients with muscle weakness/pain. Clear guidance is necessary to enable the optimal management of plasma in real-world clinical practice in patients who experience subjective AEs. In this Position Paper of the International Lipid Expert Panel (ILEP), we present a step-by-step patient-centred approach to the identification and management of SAMS with a particular focus on strategies to prevent and manage the nocebo/drucebo effect and to improve long-term compliance with lipid-lowering therapy

Evaluation of the impact of iPSC differentiation protocols on transcriptomic signatures

\ua9 2024 The Authors. Human induced pluripotent stem cells (iPSC) have the potential to produce desired target cell types in vitro and allow for the high-throughput screening of drugs/chemicals at population level thereby minimising the cost of drug discovery and drug withdrawals after clinical trials. There is a substantial need for the characterisation of the iPSC derived models to better understand and utilise them for toxicological relevant applications. In our study, iPSC (SBAD2 or SBAD3 lines obtained from StemBANCC project) were differentiated towards toxicologically relevant cell types: alveolar macrophages, brain capillary endothelial cells, brain cells, endothelial cells, hepatocytes, lung airway epithelium, monocytes, podocytes and renal proximal tubular cells. A targeted transcriptomic approach was employed to understand the effects of differentiation protocols on these cell types. Pearson correlation and principal component analysis (PCA) separated most of the intended target cell types and undifferentiated iPSC models as distinct groups with a high correlation among replicates from the same model. Based on PCA, the intended target cell types could also be separated into the three germ layer groups (ectoderm, endoderm and mesoderm). Differential expression analysis (DESeq2) presented the upregulated genes in each intended target cell types that allowed the evaluation of the differentiation to certain degree and the selection of key differentiation markers. In conclusion, these data confirm the versatile use of iPSC differentiated cell types as standardizable and relevant model systems for in vitro toxicology

Systematic review with meta-analysis: Effects of probiotic supplementation on symptoms in functional dyspepsia

The pathophysiology of functional dyspepsia (FD) remains poorly understood, but alterations of the small intestinal microbiome have been observed. The place of probiotics in treatment is uncertain. We performed a systematic review and meta-analysis of the currently available randomized, controlled trials (RCTs) to evaluate the potential beneficial effects and risks of probiotics in FD. Pubmed, EMBASE, Scopus, Web of Science and the Cochrane Controlled Trials Register were searched (up to May 2019) for RCTs evaluating the effects of probiotic supplementation compared to placebo in adults with FD. Two reviewers independently assessed eligibility, trial quality and extracted information from identified articles. To compare the effects of probiotics with placebo, risk ratios (RRs) with 95 confidence intervals (CIs) were pooled using random effects models. Six trials, including 422 participants were included but only three RCTs could be included in the meta-analysis. Lactobacillus strains showed potential positive effects in terms of improving upper gastrointestinal (GI) symptoms in patients with FD. Probiotic supplementation tended to improve global dyspepsia score (n = 3 RCTs, risk ratio RR: 1.35, 95% CI 0.99 to 1.84; P = 0.061) and bacterial composition in the GI tract. Probiotics were well tolerated without any serious adverse events. While the available data suggest that supplementation with probiotics may improve GI symptoms in patients with FD, the evidence is insufficient to draw clear conclusions regarding efficacy. Thus, high-quality RCTs are needed to establish the beneficial effects of probiotic supplementation on FD outcomes. © 2020 The Author

Effects of Single Low-Carbohydrate, High-Fat Meal Consumption on Postprandial Lipemia and Markers of Endothelial Dysfunction: A Systematic Review of Current Evidence

Postprandial lipemia (PPL) is associated with increased risk of endothelial dysfunction (ED), a precursor of atherosclerotic cardiovascular disease (ASCVD). The effects of low-carbohydrate, high-fat (LCHF) diets on ASCVD risk are uncertain; therefore, gaining a greater understanding of LCHF meals on PPL may provide valuable insights. The current systematic review investigated the effects of single LCHF meal consumption on PPL and markers of ED. CINAHL Plus, PubMed, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for key terms related to endothelial function, cardiovascular disease, glycemia, lipemia, and the postprandial state with no restriction on date. Full-text articles were independently screened by 2 reviewers, of which 16 studies were eligible to be included in the current review. All trials reported a minimum analysis of postprandial triglycerides (PPTG) following consumption of an LCHF meal (<26% of energy as carbohydrate). Results were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Single-meal macronutrient composition was found to play a key role in determining postprandial lipid and lipoprotein responses up to 8 hours post-meal. Consumption of LCHF meals increased PPTG and may contribute to ED via reduced flow-mediated dilation and increased oxidative stress; however, energy and macronutrient composition varied considerably between studies. Consumption of an LCHF meal had a negative impact on PPL based on some, but not all, single-meal studies; therefore, the contribution of LCHF meals to cardiometabolic health outcomes remains unclear. Further research is needed on specific categories of LCHF diets to establish a causal relationship between postprandial modulation of lipids/lipoproteins and impaired vascular endothelial function. PROSPERO registration no. CRD 42023398774

The impact of type of dietary protein, animal versus vegetable, in modifying cardiometabolic risk factors: A position paper from the International Lipid Expert Panel (ILEP)

Proteins play a crucial role in metabolism, in maintaining fluid and acid-base balance and antibody synthesis. Dietary proteins are important nutrients and are classified into: 1) animal proteins (meat, fish, poultry, eggs and dairy), and, 2) plant proteins (legumes, nuts and soy). Dietary modification is one of the most important lifestyle changes that has been shown to significantly decrease the risk of cardiovascular (CV) disease (CVD) by attenuating related risk factors. The CVD burden is reduced by optimum diet through replacement of unprocessed meat with low saturated fat, animal proteins and plant proteins. In view of the available evidence, it has become acceptable to emphasize the role of optimum nutrition to maintain arterial and CV health. Such healthy diets are thought to increase satiety, facilitate weight loss, and improve CV risk. Different studies have compared the benefits of omnivorous and vegetarian diets. Animal protein related risk has been suggested to be greater with red or processed meat over and above poultry, fish and nuts, which carry a lower risk for CVD. In contrast, others have shown no association of red meat intake with CVD. The aim of this expert opinion recommendation was to elucidate the different impact of animal vs vegetable protein on modifying cardiometabolic risk factors. Many observational and interventional studies confirmed that increasing protein intake, especially plant-based proteins and certain animal-based proteins (poultry, fish, unprocessed red meat low in saturated fats and low-fat dairy products) have a positive effect in modifying cardiometabolic risk factors. Red meat intake correlates with increased CVD risk, mainly because of its non-protein ingredients (saturated fats). However, the way red meat is cooked and preserved matters. Thus, it is recommended to substitute red meat with poultry or fish in order to lower CVD risk. Specific amino acids have favourable results in modifying major risk factors for CVD, such as hypertension. Apart from meat, other animal-source proteins, like those found in dairy products (especially whey protein) are inversely correlated to hypertension, obesity and insulin resistance